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Barry J Everitt - One of the best experts on this subject based on the ideXlab platform.
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2012a) Double dissociation of the dorsomedial and dorsolateral striatal control over the acquisition and performance of cocaine seeking
2016Co-Authors: Jennifer E Murray, David Belin, Barry J EverittAbstract:The present study investigated the involvement of dopamine-dependent mechanisms in the anterior dorsolateral (aDLS) and posterior dorsomedial (pDMS) striatum during the early- and late-stage performance of cocaine-seeking behavior. Rats were trained to self-administer cocaine under Continuous Reinforcement (fixed-ratio 1, FR1) with a 20-s light conditioned stimulus (CS) presented contingently upon each infusion. After a week, rats were challenged by a change in contingency to seek cocaine during a 15-min period uninfluenced by cocaine during which each response was reinforced by a 1-s CS presentation. Dopamine transmission blockade by intracranial infusions of a-flupenthixol only in the pDMS, but not in the aDLS, dose dependently reduced performance of cue-controlled cocaine seeking at the early stage of self-administration. One cohort of rats was then trained with increasing response requirements until completing 15 sessions under a second-order schedule [FI15(FR10:S)] so that cocaine-seeking performance became well established. At this stage, intra-aDLS, but not pDMS, a-flupenthixol infusions dose dependently reduced active lever presses. The second cohort of rats continued to self-administer cocaine under the FR1 schedule such that their drug intake was matched to the late-stage performance group. a-Flupenthixol in the pDMS, but not in the aDLS, again prevented the performance of cocaine seeking. These results show that dopamine transmission in the pDMS is required for initial performance of goal-directed cocaine seeking, and that its role is ultimately subverted and devolves instead to the aDLS only following training with high rates of cocaine-seeking behavior, supporting the theory o
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double dissociation of the dorsomedial and dorsolateral striatal control over the acquisition and performance of cocaine seeking
Neuropsychopharmacology, 2012Co-Authors: Barry J Everitt, Jennifer E Murray, David BelinAbstract:The present study investigated the involvement of dopamine-dependent mechanisms in the anterior dorsolateral (aDLS) and posterior dorsomedial (pDMS) striatum during the early- and late-stage performance of cocaine-seeking behavior. Rats were trained to self-administer cocaine under Continuous Reinforcement (fixed-ratio 1, FR1) with a 20-s light conditioned stimulus (CS) presented contingently upon each infusion. After a week, rats were challenged by a change in contingency to seek cocaine during a 15-min period uninfluenced by cocaine during which each response was reinforced by a 1-s CS presentation. Dopamine transmission blockade by intracranial infusions of α-flupenthixol only in the pDMS, but not in the aDLS, dose dependently reduced performance of cue-controlled cocaine seeking at the early stage of self-administration. One cohort of rats was then trained with increasing response requirements until completing 15 sessions under a second-order schedule [FI15(FR10:S)] so that cocaine-seeking performance became well established. At this stage, intra-aDLS, but not pDMS, α-flupenthixol infusions dose dependently reduced active lever presses. The second cohort of rats continued to self-administer cocaine under the FR1 schedule such that their drug intake was matched to the late-stage performance group. α-Flupenthixol in the pDMS, but not in the aDLS, again prevented the performance of cocaine seeking. These results show that dopamine transmission in the pDMS is required for initial performance of goal-directed cocaine seeking, and that its role is ultimately subverted and devolves instead to the aDLS only following training with high rates of cocaine-seeking behavior, supporting the theory of dynamic shifts in the striatal control over cocaine seeking between goal-directed and habitual performance.
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differential control over cocaine seeking behavior by nucleus accumbens core and shell
Nature Neuroscience, 2004Co-Authors: Trevor W Robbins, Barry J EverittAbstract:Nucleus accumbens (NAc) dopamine is widely implicated in mediating the reinforcing effects of drugs of abuse. However, the precise function of the NAc itself in drug self-administration has been difficult to establish. Here we show a neural double-dissociation of the behavioral processes that underlie cocaine self-administration in rats. Whereas selective excitotoxic lesions of the NAc core had only a minor effect on the acquisition of responding for cocaine under a standard schedule of Continuous Reinforcement, these lesions profoundly impaired the acquisition of drug-seeking behavior that was maintained by drug-associated conditioned reinforcers and assessed using a second-order schedule of cocaine Reinforcement. In contrast, selective excitotoxic lesions of the NAc shell did not impair drug self-administration or the acquisition of cocaine-seeking, but they did attenuate the psychostimulant effects of cocaine. These results further our understanding of how the NAc controls drug-seeking and drug-taking behavior.
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dopamine release in the dorsal striatum during cocaine seeking behavior under the control of a drug associated cue
The Journal of Neuroscience, 2002Co-Authors: Rutsuko Ito, Trevor W Robbins, Jeffrey W Dalley, Barry J EverittAbstract:Compulsive drug use is characterized by a pattern of drug seeking and consumption that becomes progressively habitual and less and less modifiable by external and internal factors. Although traditional views would posit that nigrostriatal dopamine (DA) neurons originating in the substantia nigra and innervating the dorsal striatum are primarily concerned with motor functions, recent studies have implicated the dorsal striatum in mediating stimulus-response (habit) learning. In this study, in vivo microdialysis in combination with a second-order schedule of cocaine Reinforcement was used to investigate the role of the dorsal striatal dopamine innervation in well established drug-seeking behavior under the control of a drug-associated cue [light conditioned stimulus (CS+)]. Rats were initially trained to self-administer cocaine under a Continuous Reinforcement schedule where a response on one of two identical levers led to a 20 sec presentation of a light CS+ and an intravenous cocaine infusion (0.75 mg/kg). The response requirement for the CS+ and cocaine was then progressively increased until stable responding was established under a second-order schedule of Reinforcement. During microdialysis, rats were presented with the cocaine-associated CS+ either noncontingently or contingent on responding during a session of cocaine-seeking behavior. The results showed a marked increase in DA release in the dorsal striatum during drug-seeking, when cocaine cues were presented contingently, but not when the same cue was presented noncontingently. These data indicate a possible involvement of the dopaminergic innervation of the dorsal striatum in well established, or habitual, cocaine-seeking behavior.
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the effects of nucleus accumbens core and shell lesions on intravenous heroin self administration and the acquisition of drug seeking behaviour under a second order schedule of heroin Reinforcement
Psychopharmacology, 2001Co-Authors: Daniel M Hutcheson, Trevor W Robbins, John A Parkinson, Barry J EverittAbstract:Rationale: Evidence has implicated the nucleus accumbens (NAcc) in drug-seeking and -taking behaviour. However, the importance of the "core" and "shell" subdivisions of the NAcc in heroin-seeking and -taking behaviour remains unclear. Objectives: To investigate the function of the NAcc core and shell in heroin self-administration and heroin-seeking behaviour. Methods: Male rats were trained to self-administer heroin (0.12 mg/kg per infusion) under a Continuous Reinforcement (CRF) schedule. After responding stabilised, rats were given excitotoxic (or sham) lesions of either the NAcc core or shell and after recovery were assessed for their retention of heroin self-administration under CRF. At this point a second-order schedule of Reinforcement was introduced, commencing at FR10 (FR1:S) and terminating at FR10 (FR10:S), in which ten lever presses resulted in presentation of the heroin-associated CS+, and completion of ten such units resulted in drug infusion. Results: Within 7 days, all groups re-acquired responding for heroin under CRF at rates similar to their pre-lesion performance. However, rats with lesions of the NAcc core, but not shell, were severely impaired in the acquisition of heroin-seeking behaviour. Conclusions: These results indicate an important role for the core of the NAcc in the acquisition of heroin-seeking behaviour under the control of drug-associated stimuli.
Mauricio R Papini - One of the best experts on this subject based on the ideXlab platform.
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partial Reinforcement in rat autoshaping with a long cs effects of pramipexole and chlordiazepoxide on sign and goal tracking
Psicológica: Revista de metodología y psicología experimental, 2021Co-Authors: Esmeralda Fuentesverdugo, Mauricio R Papini, Carmen Torres, Ricardo Pellon, Patrick AnselmeAbstract:In Pavlovian autoshaping, sign-tracking responses (lever pressing) to a conditioned stimulus (CS) are usually invigorated under partial Reinforcement (PR) compared to Continuous Reinforcement (CR). This effect, called the PR acquisition effect (PRAE), can be interpreted in terms of increased incentive hope or frustration-induced drive derived from PR training. Incentive hope and frustration have been related to dopaminergic and GABAergic activity, respectively. We examined the within-trial dynamics of sign and goal tracking in rats exposed to 20-s-long lever presentations during autoshaping acquisition under PR vs. CR conditions under the effects of drugs tapping on dopamine and GABA activity. There was no evidence of the PRAE in these results, both groups showing high, stable sign-tracking response rates. However, the pharmacological treatments affected behavior as revealed in within-trial changes. The dopamine D2 receptor agonist pramipexole (0.4 mg/kg) suppressed lever pressing and magazine entries relative to saline controls in a within-subject design, but only in PR animals. The allosteric benzodiazepine chlordiazepoxide (5 mg/kg) failed to affect either sign or goal tracking in either CR or PR animals. These results emphasize the roles of dopamine and GABA receptors in autoshaping performance, but remain inconclusive with respect to incentive hope and frustration theories. Some aspects of within-trial changes in sign and goal tracking are consistent with a mixture of reward timing and response competition.
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dorsomedial striatum lesions affect adjustment to reward uncertainty but not to reward devaluation or omission
Neuroscience, 2016Co-Authors: Carmen Torres, Amanda C Glueck, Shannon E Conrad, Ignacio Moron, Mauricio R PapiniAbstract:The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. Continuous Reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial Reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under Continuous Reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons.
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correlates of recovery from incentive downshift a preliminary selective breeding study
International Journal of Comparative Psychology, 2014Co-Authors: Leonardo A Ortega, Jacob N Norris, Florencia M Lopezseal, Thomas Ramos, Mauricio R PapiniAbstract:Rats exposed to a downshift in the concentration of a sucrose solution from 32% to 4% exhibit a transient suppression of consummatory behavior relative to an unshifted control group always exposed to 4% sucrose. One explanation of this effect, known as consummatory successive negative contrast (cSNC), explains consummatory suppression as arising from an emotional state of frustration that redirects behavior away from the source of the devalued solution. A preliminary selective breeding protocol consisting of three experiments was performed. Experiment 1 reports results from 5 generations of selected breeding for either high (H) or low (L) recovery rates from cSNC. A control line of randomly (R) mated rats was included. cSNC was reduced in H rats, but L and R rats did not differ across generations. H rats also provided no evidence of behavioral activation in acquisition or increased persistence in extinction after partial Reinforcement, rather than Continuous Reinforcement. L and R rats, by contrast, showed both of these effects. H rats were also significantly smaller in body size than R rats, but did not differ in terms of water intake, sucrose sensitivity, open-field activity, or responding to sucrose solutions before the downshift. In Experiment 2, H infants from the sixth selected generation showed increased bandwidth in vocalizations induced by mother-infant separation relative to L and R rats. Experiment 3 showed that H rats failed to show increased response to incentive downshift after treatment with the nonselective opioid antagonist naloxone, as done by L and R rats. The results, if replicated, may provide support for the interpretation of a significant role of frustration in cSNC.
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correlates of recovery from incentive downshift a preliminary selective breeding study escholarship
International Journal of Comparative Psychology, 2014Co-Authors: Leonardo A Ortega, Jacob N Norris, Florencia M Lopezseal, Thomas Ramos, Mauricio R PapiniAbstract:Rats exposed to a downshift in the concentration of a sucrose solution from 32% to 4% exhibit a transient suppression of consummatory behavior relative to an unshifted control always exposed to 4% sucrose. One explanation of this effect, known as consummatory successive negative contrast (cSNC), explains consummatory suppression as arising from an emotional state of frustration that redirects behavior away from the source of the devalued solution. A preliminary selective breeding protocol consisting of three experiments was performed. Experiment 1 reports results from 5 generations of selected breeding for either high (H) or low (L) recovery rates from cSNC. A control line of randomly (R) mated rats was included. cSNC was reduced in H rats, but L and R rats did not differ across generations. H rats also provided no evidence of behavioral activation in acquisition or increased persistence in extinction after partial Reinforcement, rather than Continuous Reinforcement. L and R rats, by contrast, showed both of these effects. H rats were also significantly smaller in body size than R rats, but did not differ in terms of water intake, sucrose sensitivity, open-field activity, or responding to sucrose solutions before the downshift. In Experiment 2, H infants from the sixth selected generation showed increased bandwidth in vocalizations induced by mother-infant separation relative to L and R rats. Experiment 3 showed that H rats failed to show increased response to incentive downshift after treatment with the nonselective opioid antagonist naloxone, as done by L and R rats. The results, if replicated, may provide support for the interpretation of a significant role of frustration in cSNC.
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role of the ventrolateral orbital cortex and medial prefrontal cortex in incentive downshift situations
Behavioural Brain Research, 2013Co-Authors: Leonardo A Ortega, Amanda C Glueck, Megan L Uhelski, Perry N Fuchs, Mauricio R PapiniAbstract:a b s t r a c t The present research evaluated the role of two prefrontal cortex areas, the ventrolateral orbital cor- tex (VLO) and the medial prefrontal cortex (mPFC), on two situations involving incentive downshifts, consummatory successive negative contrast (cSNC) with sucrose solutions and Pavlovian autoshaping following Continuous vs. partial Reinforcement with food pellets. Animals received electrolytic lesions and then were tested on cSNC, autoshaping, open-field activity, and sucrose sensitivity. Lesions of the VLO reduced suppression of consummatory behavior after the incentive downshift, but only during the first downshift trial, and also eliminated the enhancement of anticipatory behavior during partial rein- forcement, relative to Continuous Reinforcement, in autoshaping. There was no evidence of specific effects of mPFC lesions on incentive downshifts. Open-field activity was also reduced by VLO lesions, but only in the central area, whereas mPFC lesions had no observable effects on activity. Animals with mPFC lesions exhibited decreased consumption of the lowest sucrose concentration, whereas no effects were observed in animals with VLO lesions. These results suggest that the VLO may exert nonassociative (i.e., motiva- tional, emotional) influences on behavior in situations involving incentive downshifts. No clear role on incentive downshift was revealed by mPFC lesions.
Trevor W Robbins - One of the best experts on this subject based on the ideXlab platform.
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differential control over cocaine seeking behavior by nucleus accumbens core and shell
Nature Neuroscience, 2004Co-Authors: Trevor W Robbins, Barry J EverittAbstract:Nucleus accumbens (NAc) dopamine is widely implicated in mediating the reinforcing effects of drugs of abuse. However, the precise function of the NAc itself in drug self-administration has been difficult to establish. Here we show a neural double-dissociation of the behavioral processes that underlie cocaine self-administration in rats. Whereas selective excitotoxic lesions of the NAc core had only a minor effect on the acquisition of responding for cocaine under a standard schedule of Continuous Reinforcement, these lesions profoundly impaired the acquisition of drug-seeking behavior that was maintained by drug-associated conditioned reinforcers and assessed using a second-order schedule of cocaine Reinforcement. In contrast, selective excitotoxic lesions of the NAc shell did not impair drug self-administration or the acquisition of cocaine-seeking, but they did attenuate the psychostimulant effects of cocaine. These results further our understanding of how the NAc controls drug-seeking and drug-taking behavior.
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dopamine release in the dorsal striatum during cocaine seeking behavior under the control of a drug associated cue
The Journal of Neuroscience, 2002Co-Authors: Rutsuko Ito, Trevor W Robbins, Jeffrey W Dalley, Barry J EverittAbstract:Compulsive drug use is characterized by a pattern of drug seeking and consumption that becomes progressively habitual and less and less modifiable by external and internal factors. Although traditional views would posit that nigrostriatal dopamine (DA) neurons originating in the substantia nigra and innervating the dorsal striatum are primarily concerned with motor functions, recent studies have implicated the dorsal striatum in mediating stimulus-response (habit) learning. In this study, in vivo microdialysis in combination with a second-order schedule of cocaine Reinforcement was used to investigate the role of the dorsal striatal dopamine innervation in well established drug-seeking behavior under the control of a drug-associated cue [light conditioned stimulus (CS+)]. Rats were initially trained to self-administer cocaine under a Continuous Reinforcement schedule where a response on one of two identical levers led to a 20 sec presentation of a light CS+ and an intravenous cocaine infusion (0.75 mg/kg). The response requirement for the CS+ and cocaine was then progressively increased until stable responding was established under a second-order schedule of Reinforcement. During microdialysis, rats were presented with the cocaine-associated CS+ either noncontingently or contingent on responding during a session of cocaine-seeking behavior. The results showed a marked increase in DA release in the dorsal striatum during drug-seeking, when cocaine cues were presented contingently, but not when the same cue was presented noncontingently. These data indicate a possible involvement of the dopaminergic innervation of the dorsal striatum in well established, or habitual, cocaine-seeking behavior.
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the effects of nucleus accumbens core and shell lesions on intravenous heroin self administration and the acquisition of drug seeking behaviour under a second order schedule of heroin Reinforcement
Psychopharmacology, 2001Co-Authors: Daniel M Hutcheson, Trevor W Robbins, John A Parkinson, Barry J EverittAbstract:Rationale: Evidence has implicated the nucleus accumbens (NAcc) in drug-seeking and -taking behaviour. However, the importance of the "core" and "shell" subdivisions of the NAcc in heroin-seeking and -taking behaviour remains unclear. Objectives: To investigate the function of the NAcc core and shell in heroin self-administration and heroin-seeking behaviour. Methods: Male rats were trained to self-administer heroin (0.12 mg/kg per infusion) under a Continuous Reinforcement (CRF) schedule. After responding stabilised, rats were given excitotoxic (or sham) lesions of either the NAcc core or shell and after recovery were assessed for their retention of heroin self-administration under CRF. At this point a second-order schedule of Reinforcement was introduced, commencing at FR10 (FR1:S) and terminating at FR10 (FR10:S), in which ten lever presses resulted in presentation of the heroin-associated CS+, and completion of ten such units resulted in drug infusion. Results: Within 7 days, all groups re-acquired responding for heroin under CRF at rates similar to their pre-lesion performance. However, rats with lesions of the NAcc core, but not shell, were severely impaired in the acquisition of heroin-seeking behaviour. Conclusions: These results indicate an important role for the core of the NAcc in the acquisition of heroin-seeking behaviour under the control of drug-associated stimuli.
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dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine seeking behavior in rats
The Journal of Neuroscience, 2000Co-Authors: Jeffrey W Dalley, Trevor W Robbins, Simon R Howes, Barry J EverittAbstract:The dopaminergic innervation of the nucleus accumbens is generally agreed to mediate the primary reinforcing and locomotor effects of psychostimulants, but there is less consensus on conditioned dopamine (DA) release during drug-seeking behavior. We investigated the neurochemical correlates of drug-seeking behavior under the control of a drug-associated cue [a light conditioned stimulus (CS+)] and to noncontingent presentations of the CS+ in the core and shell subregions of the nucleus accumbens. Rats self-administered cocaine under a Continuous Reinforcement schedule in which a response on one of two identical levers led to an intravenous cocaine infusion (0.25 mg/infusion) and a 20 sec light CS+. Response requirements for cocaine and the CS+ were then progressively increased until stable responding was established under a second-order schedule of Reinforcement. During microdialysis, rats were presented noncontingently with a set of 10 sec CS+ and neutral tone stimuli (CS−) before and after a 90 min period during which they responded for cocaine under a second-order schedule. Results showed the following: (1) nucleus accumbens DA increased in both the core and shell during intravenous cocaine self-administration; (2) noncontingent presentations of a cocaine-associated CS+ led to increased DA release selectively in the nucleus accumbens core; and (3) extracellular DA levels were unaltered in both core and shell during a protracted period of drug-seeking behavior under the control of the same cocaine-associated cue. These results indicate that the mesolimbic dopamine system is activated after exposure to drug-associated stimuli under specific conditions.
Jennifer E Murray - One of the best experts on this subject based on the ideXlab platform.
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2012a) Double dissociation of the dorsomedial and dorsolateral striatal control over the acquisition and performance of cocaine seeking
2016Co-Authors: Jennifer E Murray, David Belin, Barry J EverittAbstract:The present study investigated the involvement of dopamine-dependent mechanisms in the anterior dorsolateral (aDLS) and posterior dorsomedial (pDMS) striatum during the early- and late-stage performance of cocaine-seeking behavior. Rats were trained to self-administer cocaine under Continuous Reinforcement (fixed-ratio 1, FR1) with a 20-s light conditioned stimulus (CS) presented contingently upon each infusion. After a week, rats were challenged by a change in contingency to seek cocaine during a 15-min period uninfluenced by cocaine during which each response was reinforced by a 1-s CS presentation. Dopamine transmission blockade by intracranial infusions of a-flupenthixol only in the pDMS, but not in the aDLS, dose dependently reduced performance of cue-controlled cocaine seeking at the early stage of self-administration. One cohort of rats was then trained with increasing response requirements until completing 15 sessions under a second-order schedule [FI15(FR10:S)] so that cocaine-seeking performance became well established. At this stage, intra-aDLS, but not pDMS, a-flupenthixol infusions dose dependently reduced active lever presses. The second cohort of rats continued to self-administer cocaine under the FR1 schedule such that their drug intake was matched to the late-stage performance group. a-Flupenthixol in the pDMS, but not in the aDLS, again prevented the performance of cocaine seeking. These results show that dopamine transmission in the pDMS is required for initial performance of goal-directed cocaine seeking, and that its role is ultimately subverted and devolves instead to the aDLS only following training with high rates of cocaine-seeking behavior, supporting the theory o
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double dissociation of the dorsomedial and dorsolateral striatal control over the acquisition and performance of cocaine seeking
Neuropsychopharmacology, 2012Co-Authors: Barry J Everitt, Jennifer E Murray, David BelinAbstract:The present study investigated the involvement of dopamine-dependent mechanisms in the anterior dorsolateral (aDLS) and posterior dorsomedial (pDMS) striatum during the early- and late-stage performance of cocaine-seeking behavior. Rats were trained to self-administer cocaine under Continuous Reinforcement (fixed-ratio 1, FR1) with a 20-s light conditioned stimulus (CS) presented contingently upon each infusion. After a week, rats were challenged by a change in contingency to seek cocaine during a 15-min period uninfluenced by cocaine during which each response was reinforced by a 1-s CS presentation. Dopamine transmission blockade by intracranial infusions of α-flupenthixol only in the pDMS, but not in the aDLS, dose dependently reduced performance of cue-controlled cocaine seeking at the early stage of self-administration. One cohort of rats was then trained with increasing response requirements until completing 15 sessions under a second-order schedule [FI15(FR10:S)] so that cocaine-seeking performance became well established. At this stage, intra-aDLS, but not pDMS, α-flupenthixol infusions dose dependently reduced active lever presses. The second cohort of rats continued to self-administer cocaine under the FR1 schedule such that their drug intake was matched to the late-stage performance group. α-Flupenthixol in the pDMS, but not in the aDLS, again prevented the performance of cocaine seeking. These results show that dopamine transmission in the pDMS is required for initial performance of goal-directed cocaine seeking, and that its role is ultimately subverted and devolves instead to the aDLS only following training with high rates of cocaine-seeking behavior, supporting the theory of dynamic shifts in the striatal control over cocaine seeking between goal-directed and habitual performance.
David Belin - One of the best experts on this subject based on the ideXlab platform.
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2012a) Double dissociation of the dorsomedial and dorsolateral striatal control over the acquisition and performance of cocaine seeking
2016Co-Authors: Jennifer E Murray, David Belin, Barry J EverittAbstract:The present study investigated the involvement of dopamine-dependent mechanisms in the anterior dorsolateral (aDLS) and posterior dorsomedial (pDMS) striatum during the early- and late-stage performance of cocaine-seeking behavior. Rats were trained to self-administer cocaine under Continuous Reinforcement (fixed-ratio 1, FR1) with a 20-s light conditioned stimulus (CS) presented contingently upon each infusion. After a week, rats were challenged by a change in contingency to seek cocaine during a 15-min period uninfluenced by cocaine during which each response was reinforced by a 1-s CS presentation. Dopamine transmission blockade by intracranial infusions of a-flupenthixol only in the pDMS, but not in the aDLS, dose dependently reduced performance of cue-controlled cocaine seeking at the early stage of self-administration. One cohort of rats was then trained with increasing response requirements until completing 15 sessions under a second-order schedule [FI15(FR10:S)] so that cocaine-seeking performance became well established. At this stage, intra-aDLS, but not pDMS, a-flupenthixol infusions dose dependently reduced active lever presses. The second cohort of rats continued to self-administer cocaine under the FR1 schedule such that their drug intake was matched to the late-stage performance group. a-Flupenthixol in the pDMS, but not in the aDLS, again prevented the performance of cocaine seeking. These results show that dopamine transmission in the pDMS is required for initial performance of goal-directed cocaine seeking, and that its role is ultimately subverted and devolves instead to the aDLS only following training with high rates of cocaine-seeking behavior, supporting the theory o
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double dissociation of the dorsomedial and dorsolateral striatal control over the acquisition and performance of cocaine seeking
Neuropsychopharmacology, 2012Co-Authors: Barry J Everitt, Jennifer E Murray, David BelinAbstract:The present study investigated the involvement of dopamine-dependent mechanisms in the anterior dorsolateral (aDLS) and posterior dorsomedial (pDMS) striatum during the early- and late-stage performance of cocaine-seeking behavior. Rats were trained to self-administer cocaine under Continuous Reinforcement (fixed-ratio 1, FR1) with a 20-s light conditioned stimulus (CS) presented contingently upon each infusion. After a week, rats were challenged by a change in contingency to seek cocaine during a 15-min period uninfluenced by cocaine during which each response was reinforced by a 1-s CS presentation. Dopamine transmission blockade by intracranial infusions of α-flupenthixol only in the pDMS, but not in the aDLS, dose dependently reduced performance of cue-controlled cocaine seeking at the early stage of self-administration. One cohort of rats was then trained with increasing response requirements until completing 15 sessions under a second-order schedule [FI15(FR10:S)] so that cocaine-seeking performance became well established. At this stage, intra-aDLS, but not pDMS, α-flupenthixol infusions dose dependently reduced active lever presses. The second cohort of rats continued to self-administer cocaine under the FR1 schedule such that their drug intake was matched to the late-stage performance group. α-Flupenthixol in the pDMS, but not in the aDLS, again prevented the performance of cocaine seeking. These results show that dopamine transmission in the pDMS is required for initial performance of goal-directed cocaine seeking, and that its role is ultimately subverted and devolves instead to the aDLS only following training with high rates of cocaine-seeking behavior, supporting the theory of dynamic shifts in the striatal control over cocaine seeking between goal-directed and habitual performance.