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Lane J Wallace - One of the best experts on this subject based on the ideXlab platform.
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importance of environmental context in the development of amphetamine or Apomorphine induced stereotyped behavior after single and multiple doses
Pharmacology Biochemistry and Behavior, 2000Co-Authors: John J Battisti, Norman J Uretsky, Lane J WallaceAbstract:The present study was designed to determine whether single and repeated pretreatment regimens with amphetamine or Apomorphine differ in the context-dependency of sensitization of stereotyped behavior. Male CF-1 mice that were pretreated with a single high dose of amphetamine (14 mg/kg intraperitoneally [IP]) or Apomorphine (40 mg/kg subcutaneously [SC]) only became sensitized to a lower test dose of amphetamine (7 mg/kg IP) or Apomorphine (3 mg/kg SC) when placed in an environment that was the same as the pretreatment environment. However, animals pretreated with 3 high doses (24-h apart) of amphetamine (14 mg/kg IP) or Apomorphine (40 mg/kg SC) did demonstrate sensitization to a lower test dose of amphetamine (7 mg/kg IP) or Apomorphine (3 mg/kg SC) when placed in an environment that was different from the pretreatment environment. Context-dependent sensitization, but not context-independent sensitization, was extinguished by pairing the test environment with saline injections instead of drug injections. In addition, it was determined that neither sensitization model could be related to pharmacokinetic factors. Therefore, the results indicate that repeated exposure to amphetamine or Apomorphine overcomes the context-dependent component of sensitization of amphetamine- or Apomorphine-induced stereotyped behavior.
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sensitization of Apomorphine induced stereotyped behavior in mice is context dependent
Psychopharmacology, 1999Co-Authors: John J Battisti, Norman J Uretsky, Lane J WallaceAbstract:Rationale: The role of the environment in the sensitization of the stereotyped behavioral effects of Apomorphine is unclear, since sensitization of this drug effect has either been difficult to demonstrate or has been shown to occur with a low but not a higher dose of Apomorphine. Objectives: The present study was designed to determine whether sensitization of the stereotyped behavioral effects induced by a single dose of Apomorphine is dependent on environmental context. Methods: CF-1 mice were pretreated with Apomorphine or vehicle under different environmental conditions and tested for stereotyped behavior after Apomorphine challenge. Animals were scored positively for stereotyped behavior if they remained stationary and exhibited repetitive head and/or fore-limb movements, and data are reported as the percentage of mice rated as positive for stereotyped behavior. Results: When mice were pretreated with 40 mg/kg Apomorphine and later tested in the same environment, the dose–response curve for stereotyped behavior elicited by Apomorphine was shifted threefold to the left 48 h after pretreatment, and this sensitization persisted for at least 28 days after pretreatment. Mice pretreated with Apomorphine did not have higher brain levels of Apomorphine after administration of the test dose of Apomorphine. When the pretreatment environment was different from the test environment, mice did not exhibit sensitization to Apomorphine. Conclusions: These results show that pre-exposure to a single high dose of Apomorphine induces a long-lasting sensitization of Apomorphine-induced stereotyped behavior that is context dependent. Since Apomorphine directly activates dopamine receptors, these observations suggest that a mechanism located postsynaptic to dopamine neurons may be responsible for sensitization of stereotyped behavior.
Alexander R. Cools - One of the best experts on this subject based on the ideXlab platform.
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Cocaine strongly reduces prepulse inhibition in Apomorphine-susceptible rats, but not in Apomorphine-unsusceptible rats: Regulation by dopamine D2 receptors
Behavioural Brain Research, 2006Co-Authors: Martine C. J. Van Der Elst, Bart A. Ellenbroek, Alexander R. CoolsAbstract:Abstract Dopaminergic agonists, such as Apomorphine and amphetamine, have been shown to drastically reduce prepulse inhibition of the acoustic startle reflex. The effects of the indirect dopamine agonist cocaine on prepulse inhibition have only been described in a few reports and have yielded conflicting results, possibly due to individual differences within and between rat strains. In this study we therefore used Apomorphine-susceptible and Apomorphine-unsusceptible rats, as an animal model for individual differences, to study the effects of cocaine (20, 30 mg/kg i.p.) on prepulse inhibition. In addition we tested whether the cocaine-induced deficit in prepulse inhibition could be reversed by the D2-antagonist remoxipride (5 mg/kg i.p.), the alpha-1 adrenoceptor antagonist prazosin (2.5 mg/kg i.p.) and the 5-HT2-antagonist ketanserin (2.0 mg/kg i.p.). Cocaine strongly reduced prepulse inhibition in Apomorphine-susceptible rats, but had no effect at all on Apomorphine-unsusceptible rats. Remoxipride had no effect on prepulse inhibition, but prazosin and ketanserin increased prepulse inhibition. Both remoxipride and prazosin reversed the cocaine-induced deficit in prepulse inhibition, whereas ketanserin did not. We conclude that Apomorphine-susceptible rats are extremely sensitive to the effects of cocaine on prepulse inhibition, while Apomorphine-unsusceptible rats are not. The effects of cocaine on prepulse inhibition in Apomorphine-susceptible rats were mediated by D2-receptors, but not by 5-HT2-receptors or alpha-1 adrenoceptors.
Marinete Pinheiro Carrera - One of the best experts on this subject based on the ideXlab platform.
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repeated pre trial and post trial low and high dose Apomorphine treatments induce comparable inhibitory excitatory sensitization and conditioned drug effects
Pharmacology Biochemistry and Behavior, 2018Co-Authors: Breno Garone Santos, Robert J Carey, Marinete Pinheiro CarreraAbstract:Abstract This investigation was undertaken to compare the sensitization/conditioned effects induced by Apomorphine given pre-trial versus administered immediately post-trial or 15 min post-trial. We measured the effects on locomotor activity of 5 daily Apomorphine treatments induced by an inhibitory low auto-receptor dose (0.05 mg/kg) and a stimulatory high postsynaptic dose (2.0 mg/kg). Three sets of four groups were used and each set of four groups was comprised of two vehicle and two Apomorphine groups (0.05/2.0 Apomorphine). The only difference among the three sets of four groups was when the treatments were administered relative to placement in the novel environment. One set received the treatment pre-test, another set was injected immediately after and the third set injected 15 min after 5 min test sessions in a novel environment. The repeated pre and immediate post-test Apomorphine treatments induced locomotor sensitization over the 5 days of treatment. The low dose pre and immediate post-test treatments progressively decreased locomotion and the high dose pre and immediate post-test progressively increased locomotion. Critically, the tests for the immediate post-test groups were non-drug and for both the pre-test and immediate post-test groups, sensitization effects did not occur until the second test day. To control for non-associative Apomorphine effects, the same Apomorphine treatments were given post-test after a 15 minute delay and were found to be equivalent to vehicle. In a subsequent conditioning test, both the pre and immediate post-test low dose Apomorphine groups showed conditioned behavioral inhibition and the pre and immediate post-test high dose Apomorphine groups showed conditioned behavioral stimulation. We propose that the inhibitory low dose Apomorphine decreased the salience/incentive of the novel environment association and thereby decreased the behavioral response and conversely that the high dose excitatory Apomorphine treatment increased the salience/incentive value of the novel environment association and potentiated the behavioral response.
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drug memory substitution during re consolidation a single inhibitory autoreceptor Apomorphine treatment given during psychostimulant memory re consolidation replaces psychostimulant conditioning with conditioned inhibition and reverses psychostimulan
Behavioural Brain Research, 2014Co-Authors: Joao Marcos De Mello Bastos, Flavia Regina Cruz Dias, Robert J Carey, Victor Hugo Nicacio Alves, Marinete Pinheiro CarreraAbstract:Abstract Psychostimulant conditioning and sensitization effects have proven to be difficult to eliminate using behavioral methods. We used a low autoreceptor dose of Apomorphine in counter-conditioning and memory re-consolidation protocols to modify conditioned and sensitized responses induced by a high dose of Apomorphine. Rats received five daily treatments of Apomorphine (2.0 mg/kg) and were tested in an arena for 30 min to induce conditioning and sensitization. Conditioning was validated in a brief 5 min non-drug conditioning test and sensitization by a 2.0 Apomorphine challenge test. Next, the counter-conditioning and memory re-consolidation protocols were initiated. In counter-conditioning, vehicle or 0.05 mg/kg Apomorphine was given either 15 min or immediately before a 5 min arena test. In the memory re-consolidation protocol, the vehicle and 0.05 Apomorphine treatments were administered post-trial either immediately after or 15 min after the 5 min arena test. Effects were assessed with a 5 min saline conditioning test and a second 2.0 mg/kg Apomorphine challenge test. The counter-conditioning protocol induced hypolocomotion and but did not induce a conditioned hypo-locomotion and did not alter the sensitized response. The 15 min post-trial treatment did not affect either the conditioned or the sensitized responses. The immediate post-trial treatment eliminated sensitization and induced a conditioned hypoactivity response. These results highlight the memory re-consolidation period as a critical target for drug memory substitution and suggest the potential utility of the pharmacological inhibition of dopamine activity given as a therapeutic drug memory replacement during addictive drug memory re-consolidation.
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reversal of Apomorphine locomotor sensitization by a single post conditioning trial treatment with a low autoreceptor dose of Apomorphine a memory re consolidation approach
Pharmacology Biochemistry and Behavior, 2011Co-Authors: Marinete Pinheiro Carrera, Robert J Carey, Flavia Regina Cruz Dias, Liana Wermelinger De MatosAbstract:Abstract Sensitization is a common feature of psychostimulants and sensitization effects are generally considered to be linked to the addictive properties of these drugs. We used a conventional paired/unpaired Pavlovian protocol to induce a context specific sensitization to the locomotor stimulant effect of a high dose of Apomorphine (2.0 mg/kg). Two days following a 5 session sensitization induction phase, a brief 5 min non-drug test for conditioning was conducted. Only the paired groups exhibited locomotor stimulant conditioned response effects. Immediately following this brief test for conditioning, the paired and the unpaired groups received injections of 0.05 mg/kg Apomorphine, 2.0 mg/kg Apomorphine or vehicle designed to differentially impact memory re-consolidation of the conditioning. Two days later, all groups received a sensitization challenge test with 2.0 mg/kg Apomorphine. The 2.0 mg/kg Apomorphine post-trial treatment potentiated sensitization while the 0.05 mg/kg eliminated sensitization. These effects were only observed in the paired groups. The activation of dopaminergic systems by the high dose of Apomorphine strengthened the drug/environment association whereas the inhibition of dopamine activity by the low auto-receptor dose eliminated this association. The results point to the importance of conditioning to context specific sensitization and targeting memory re-consolidation of conditioning as a paradigm to modify sensitization.
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drug conditioning induced by intrastriatal Apomorphine administration
Brain Research, 1998Co-Authors: Marinete Pinheiro Carrera, Fabiola C R Brunhara, Rainer K W Schwarting, Carlos TomazAbstract:The present study examined (1) whether the neostriatum is involved in a drug-induced conditioned locomotor response and; (2) whether this structure participates in the development of behavioral sensitization. Moreover, the present study addressed the question whether the development of behavioral sensitization is necessary for the induction of conditioning. Rats received injections of either Apomorphine (2 μg) or vehicle (solution of 0.1% ascorbate/saline) into the dorsal neostriatum daily for 7 days. These treatments were performed immediately prior to (Apomorphine-paired group and vehicle group) or 30 min following (Apomorphine-unpaired group) 10-min placement in an open field which served as the test environment. After a 3-day drug withdrawal period, the animals were given a 10-min non-drug vehicle test trial in the test environment. Three days later, a drug test with Apomorphine was administered to the animals of the paired and unpaired treatment groups; the vehicle group again received an injection of vehicle. The analysis of locomotor activity in the open field (measured as the distance traversed) revealed that locomotor activity in the Apomorphine-paired group was higher than in the other groups. There were no indications for behavioral sensitization to intrastriatal Apomorphine, since the locomotor response in the Apomorphine-paired group did not increase, but rather decreased with daily repeated injections of Apomorphine. Furthermore, only the Apomorphine-paired animals showed a higher locomotor response when tested after an intrastriatal injection of vehicle in the previously Apomorphine-paired environment, which is indicative of a conditioned drug effect. These results suggest that the neostriatum is directly involved in the development of drug-induced conditioning of locomotor behavior but not in the establishment of behavioral sensitization.
John J Battisti - One of the best experts on this subject based on the ideXlab platform.
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importance of environmental context in the development of amphetamine or Apomorphine induced stereotyped behavior after single and multiple doses
Pharmacology Biochemistry and Behavior, 2000Co-Authors: John J Battisti, Norman J Uretsky, Lane J WallaceAbstract:The present study was designed to determine whether single and repeated pretreatment regimens with amphetamine or Apomorphine differ in the context-dependency of sensitization of stereotyped behavior. Male CF-1 mice that were pretreated with a single high dose of amphetamine (14 mg/kg intraperitoneally [IP]) or Apomorphine (40 mg/kg subcutaneously [SC]) only became sensitized to a lower test dose of amphetamine (7 mg/kg IP) or Apomorphine (3 mg/kg SC) when placed in an environment that was the same as the pretreatment environment. However, animals pretreated with 3 high doses (24-h apart) of amphetamine (14 mg/kg IP) or Apomorphine (40 mg/kg SC) did demonstrate sensitization to a lower test dose of amphetamine (7 mg/kg IP) or Apomorphine (3 mg/kg SC) when placed in an environment that was different from the pretreatment environment. Context-dependent sensitization, but not context-independent sensitization, was extinguished by pairing the test environment with saline injections instead of drug injections. In addition, it was determined that neither sensitization model could be related to pharmacokinetic factors. Therefore, the results indicate that repeated exposure to amphetamine or Apomorphine overcomes the context-dependent component of sensitization of amphetamine- or Apomorphine-induced stereotyped behavior.
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sensitization of Apomorphine induced stereotyped behavior in mice is context dependent
Psychopharmacology, 1999Co-Authors: John J Battisti, Norman J Uretsky, Lane J WallaceAbstract:Rationale: The role of the environment in the sensitization of the stereotyped behavioral effects of Apomorphine is unclear, since sensitization of this drug effect has either been difficult to demonstrate or has been shown to occur with a low but not a higher dose of Apomorphine. Objectives: The present study was designed to determine whether sensitization of the stereotyped behavioral effects induced by a single dose of Apomorphine is dependent on environmental context. Methods: CF-1 mice were pretreated with Apomorphine or vehicle under different environmental conditions and tested for stereotyped behavior after Apomorphine challenge. Animals were scored positively for stereotyped behavior if they remained stationary and exhibited repetitive head and/or fore-limb movements, and data are reported as the percentage of mice rated as positive for stereotyped behavior. Results: When mice were pretreated with 40 mg/kg Apomorphine and later tested in the same environment, the dose–response curve for stereotyped behavior elicited by Apomorphine was shifted threefold to the left 48 h after pretreatment, and this sensitization persisted for at least 28 days after pretreatment. Mice pretreated with Apomorphine did not have higher brain levels of Apomorphine after administration of the test dose of Apomorphine. When the pretreatment environment was different from the test environment, mice did not exhibit sensitization to Apomorphine. Conclusions: These results show that pre-exposure to a single high dose of Apomorphine induces a long-lasting sensitization of Apomorphine-induced stereotyped behavior that is context dependent. Since Apomorphine directly activates dopamine receptors, these observations suggest that a mechanism located postsynaptic to dopamine neurons may be responsible for sensitization of stereotyped behavior.
Bart A. Ellenbroek - One of the best experts on this subject based on the ideXlab platform.
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effect of Apomorphine on cognitive performance and sensorimotor gating in humans
Psychopharmacology, 2010Co-Authors: A F A Schellekens, Bart A. Ellenbroek, Koen P Grootens, Cees Neef, K L L Movig, Jan K Buitelaar, R J VerkesAbstract:Introduction Dysfunction of brain dopamine systems is involved in various neuropsychiatric disorders. Challenge studies with dopamine receptor agonists have been performed to assess dopamine receptor functioning, classically using the release of growth hormone (GH) from the hindbrain as primary outcome measure. The objective of the current study was to assess dopamine receptor functioning at the forebrain level. Methods Fifteen healthy male volunteers received Apomorphine sublingually (2 mg), subcutaneously (0.005 mg/kg), and placebo in a balanced, double-blind, cross-over design. Outcome measures were plasma GH levels, performance on an AX continuous performance test, and prepulse inhibition of the acoustic startle. The relation between central outcome measures and Apomorphine levels observed in plasma and calculated in the brain was modeled using a two-compartmental pharmacokinetic-pharmacodynamic analysis. Results After administration of Apomorphine, plasma GH increased and performance on the AX continuous performance test deteriorated, particularly in participants with low baseline performance. Apomorphine disrupted prepulse inhibition (PPI) on high-intensity (85 dB) prepulse trials and improved PPI on low intensity (75 dB) prepulse trials, particularly in participants with low baseline PPI. High cognitive performance at baseline was associated with reduced baseline sensorimotor gating. Neurophysiological measures correlated best with calculated brain Apomorphine levels after subcutaneous administration. Conclusion The Apomorphine challenge test appears a useful tool to assess dopamine receptor functioning at the forebrain level. Modulation of the effect of Apomorphine by baseline performance levels may be explained by an inverted U-shape relation between prefrontal dopamine functioning and cognitive performance, and mesolimbic dopamine functioning and sensorimotor gating. Future Apomorphine challenge tests preferentially use multiple outcome measures, after subcutaneous administration of Apomorphine.
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Cocaine strongly reduces prepulse inhibition in Apomorphine-susceptible rats, but not in Apomorphine-unsusceptible rats: Regulation by dopamine D2 receptors
Behavioural Brain Research, 2006Co-Authors: Martine C. J. Van Der Elst, Bart A. Ellenbroek, Alexander R. CoolsAbstract:Abstract Dopaminergic agonists, such as Apomorphine and amphetamine, have been shown to drastically reduce prepulse inhibition of the acoustic startle reflex. The effects of the indirect dopamine agonist cocaine on prepulse inhibition have only been described in a few reports and have yielded conflicting results, possibly due to individual differences within and between rat strains. In this study we therefore used Apomorphine-susceptible and Apomorphine-unsusceptible rats, as an animal model for individual differences, to study the effects of cocaine (20, 30 mg/kg i.p.) on prepulse inhibition. In addition we tested whether the cocaine-induced deficit in prepulse inhibition could be reversed by the D2-antagonist remoxipride (5 mg/kg i.p.), the alpha-1 adrenoceptor antagonist prazosin (2.5 mg/kg i.p.) and the 5-HT2-antagonist ketanserin (2.0 mg/kg i.p.). Cocaine strongly reduced prepulse inhibition in Apomorphine-susceptible rats, but had no effect at all on Apomorphine-unsusceptible rats. Remoxipride had no effect on prepulse inhibition, but prazosin and ketanserin increased prepulse inhibition. Both remoxipride and prazosin reversed the cocaine-induced deficit in prepulse inhibition, whereas ketanserin did not. We conclude that Apomorphine-susceptible rats are extremely sensitive to the effects of cocaine on prepulse inhibition, while Apomorphine-unsusceptible rats are not. The effects of cocaine on prepulse inhibition in Apomorphine-susceptible rats were mediated by D2-receptors, but not by 5-HT2-receptors or alpha-1 adrenoceptors.