The Experts below are selected from a list of 1734 Experts worldwide ranked by ideXlab platform

Vincenzo Cuomo - One of the best experts on this subject based on the ideXlab platform.

  • wag rij rats show a reduced expression of CB1 Receptors in thalamic nuclei and respond to the CB1 Receptor Agonist r win55 212 2 with a reduced incidence of spike wave discharges
    Epilepsia, 2010
    Co-Authors: Clementina M. Van Rijn, Vincenzo Cuomo, Silvana Gaetani, Ines Santolini, Aleksandra Badura, Aleksandra Gabova, Jin Fu, Masashiko Watanabe, Gilles Van Luijtelaar, Ferdinando Nicoletti
    Abstract:

    Purpose: Genetically epileptic WAG/Rij rats develop spontaneous absence-like seizures after 3 months of age. We used WAG/Rij rats to examine whether absence seizures are associated with changes in the expression of type-1 cannabinoid (CB1) Receptors. Methods: Receptor expression was examined by in situ hybridization and western blot analysis in various brain regions of “presymptomatic” 2-month old and “symptomatic” 8-month-old WAG/Rij rats relative to age-matched nonepileptic control rats. Furthermore, we examined whether pharmacologic activation of CB1 Receptor affects absence seizures. We recorded spontaneous spike-wave discharges (SWDs) in 8-month old WAG/Rij rats systemically injected with the potent CB1 Receptor Agonist, R(+)WIN55,212-2 (3–12 mg/kg, s.c.), given alone or combined with the CB1 Receptor antAgonist/inverse Agonist, AM251 (12 mg/kg, s.c.). Results: Data showed a reduction of CB1 Receptor mRNA and protein levels in the reticular thalamic nucleus, and a reduction in CB1 Receptor protein levels in ventral basal thalamic nuclei of 8-month-old WAG/Rij rats, as compared with age-matched ACI control rats. In vivo, R(+)WIN55,212-2 caused a dose-dependent reduction in the frequency of SWDs in the first 3 h after the injection. This was followed by a late increase in the mean SWD duration, which suggests a biphasic modulation of SWDs by CB1 Receptor Agonists. Both effects were reversed or attenuated when R(+)WIN55,212-2 was combined with AM251. Discussion: These data indicate that the development of absence seizures is associated with plastic modifications of CB1 Receptors within the thalamic-cortical-thalamic network, and raise the interesting possibility that CB1 Receptors are targeted by novel antiabsence drugs.

  • WAG/Rij rats show a reduced expression of CB1 Receptors in thalamic nuclei and respond to the CB1 Receptor Agonist, R(+)WIN55,212-2, with a reduced incidence of spike-wave discharges
    Epilepsia, 2010
    Co-Authors: Clementina M. Van Rijn, Vincenzo Cuomo, Silvana Gaetani, Ines Santolini, Aleksandra Badura, Aleksandra Gabova, Jin Fu, Masashiko Watanabe, Gilles Van Luijtelaar, Ferdinando Nicoletti
    Abstract:

    Purpose: Genetically epileptic WAG/Rij rats develop spontaneous absence-like seizures after 3 months of age. We used WAG/Rij rats to examine whether absence seizures are associated with changes in the expression of type-1 cannabinoid (CB1) Receptors. Methods: Receptor expression was examined by in situ hybridization and western blot analysis in various brain regions of “presymptomatic” 2-month old and “symptomatic” 8-month-old WAG/Rij rats relative to age-matched nonepileptic control rats. Furthermore, we examined whether pharmacologic activation of CB1 Receptor affects absence seizures. We recorded spontaneous spike-wave discharges (SWDs) in 8-month old WAG/Rij rats systemically injected with the potent CB1 Receptor Agonist, R(+)WIN55,212-2 (3–12 mg/kg, s.c.), given alone or combined with the CB1 Receptor antAgonist/inverse Agonist, AM251 (12 mg/kg, s.c.). Results: Data showed a reduction of CB1 Receptor mRNA and protein levels in the reticular thalamic nucleus, and a reduction in CB1 Receptor protein levels in ventral basal thalamic nuclei of 8-month-old WAG/Rij rats, as compared with age-matched ACI control rats. In vivo, R(+)WIN55,212-2 caused a dose-dependent reduction in the frequency of SWDs in the first 3 h after the injection. This was followed by a late increase in the mean SWD duration, which suggests a biphasic modulation of SWDs by CB1 Receptor Agonists. Both effects were reversed or attenuated when R(+)WIN55,212-2 was combined with AM251. Discussion: These data indicate that the development of absence seizures is associated with plastic modifications of CB1 Receptors within the thalamic-cortical-thalamic network, and raise the interesting possibility that CB1 Receptors are targeted by novel antiabsence drugs.

  • endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory
    Proceedings of the National Academy of Sciences of the United States of America, 2009
    Co-Authors: Patrizia Campolongo, Benno Roozendaal, Viviana Trezza, Daniela Hauer, Gustav Schelling, James L Mcgaugh, Vincenzo Cuomo
    Abstract:

    Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 Receptors, the present experiments investigated whether the endocannabinoid system in the BLA influences memory consolidation and whether glucocorticoids interact with this system. The CB1 Receptor Agonist WIN55,212-2 (5–50 ng per 0.2 μL per side), infused bilaterally into the BLA of male Sprague–Dawley rats immediately after inhibitory avoidance training, induced dose-dependent enhancement of 48-h retention. Conversely, the CB1 Receptor antAgonist AM251 (0.07–0.28 ng per 0.2 μL per side) administered after training into the BLA induced inhibitory avoidance retention impairment. Furthermore, intra-BLA infusions of a low and nonimpairing dose of AM251 (0.14 ng per 0.2 μL per side) blocked the memory enhancement induced by concurrent administration of WIN55,212-2. Delayed infusions of WIN55,212-2 or AM251 administered into the BLA 3 h after training or immediate posttraining infusions of these drugs into the adjacent central amygdala did not significantly alter retention performance. Last, intra-BLA infusions of a low and otherwise nonimpairing dose of AM251 (0.14 ng per 0.2 μL per side) blocked the memory-enhancing effect induced by systemic administration of corticosterone (3 mg/kg, s.c.). These findings indicate that endocannabinoids in the BLA enhance memory consolidation and suggest that CB1 activity within this brain region is required for enabling glucocorticoid effects on memory consolidation enhancement.

  • Prenatal exposure to the cannabinoid Receptor Agonist WIN 55,212-2 increases glutamate uptake through overexpression of GLT1 and EAAC1 glutamate transporter subtypes in rat frontal cerebral cortex
    Neuropharmacology, 2007
    Co-Authors: Pasqualina Castaldo, Tiziana Antonelli, Tommaso Cassano, Silvana Gaetani, Simona Magi, Luca Ferraro, Salvatore Amoroso, Vincenzo Cuomo
    Abstract:

    Abstract Prenatal exposure to the CB1 Receptor Agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone) mesylate (WIN) at a daily dose of 0.5 mg/kg, and Δ9-tetrahydrocannabinol (Δ9-THC) at a daily dose of 5 mg/kg, reduced dialysate glutamate levels in frontal cerebral cortex of adolescent offspring (40-day-old) with respect to those born from vehicle-treated mothers. WIN treatment induced a statistically significant enhancement of Vmax l -[3H]glutamate uptake, whereas it did not modify glutamate Km, in frontal cerebral cortex synaptosomes of adolescent rats. Western blotting analysis, performed either in membrane proteins derived from homogenates and in proteins extracted from synaptosomes of frontal cerebral cortex, revealed that prenatal WIN exposure enhanced the expression of glutamate transporter 1 (GLT1) and excitatory amino acid carrier 1 (EAAC1). Moreover, immunocytochemical analyses of frontal cortex area revealed a more intense GLT1 and EAAC1 immunoreactivity (ir) distribution in the WIN-treated group. Collectively these results show that prenatal exposure to the cannabinoid CB1 Receptor Agonist WIN increases expression and functional activity of GLT1 and EAAC1 glutamate transporters (GluTs) associated to a decrease of cortical glutamate outflow, in adolescent rats. These findings may contribute to explain the mechanism underlying the cognitive impairment observed in the offspring of mothers who used marijuana during pregnancy.

  • prenatal exposure to the CB1 Receptor Agonist win 55 212 2 causes learning disruption associated with impaired cortical nmda Receptor function and emotional reactivity changes in rat offspring
    Cerebral Cortex, 2005
    Co-Authors: Tiziana Antonelli, Sergio Tanganelli, Maria Cristina Tomasini, Maria Tattoli, Tommaso Cassano, Simone Finetti, Elisa Mazzoni, Luigia Trabace, Luca Steardo, Vincenzo Cuomo
    Abstract:

    The aim of this study was to investigate whether prenatal exposure to the cannabinoid CB1 Receptor Agonist WIN 55,212-2 (WIN) at a daily dose devoid of overt signs of toxicity and/or gross malformations (0.5 mg/kg, gestation days 5--20), influences cortical glutamatergic neurotransmission, learning and emotional reactivity in rat offspring. Basal and K 1 -evoked extracellular glutamate levels were significantly lower in cortical cell cultures obtained from pups exposed to WIN during gestation with respect to those measured in cultures obtained from neonates born from vehicle-treated dams. The addition of NMDA to cortical cell cultures from neonates born from vehicle-treated dams concentration-dependently increased glutamate levels, and this was absent in cell cultures obtained from WIN-exposed pups. WIN-exposed rats also revealed a poorer performance in homing (10--12 days of age) and active avoidance tests (80 days of age) as well as a decrease in the rate of separationinduced ultrasonic emission (10 days of age). Finally, prenatal exposure to WIN induced a reduction in the number of cortical neuronal population. These findings (i) provide evidence for a deficit in cortical glutamatergic neurotransmission and behaviour in the rat neonatefollowingprenatalexposuretoWIN;and(ii)suggestthatthe reduction in cortical glutamatergic neurotransmission, NMDA Receptor activity and alterations in neuronal development might underlie, at least in part, the learning deficit and decreased emotional reactivity observed in the offspring.

Walter Fratta - One of the best experts on this subject based on the ideXlab platform.

  • CB1 Receptor Agonist and heroin but not cocaine reinstate cannabinoid seeking behaviour in the rat
    British Journal of Pharmacology, 2004
    Co-Authors: Sabrina M Spano, Liana Fattore, G Cossu, Walter Fratta, Serena Deiana, Paola Fadda
    Abstract:

    We recently provided evidence for a functional link between cannabinoid and opioid endogenous systems in relapse to heroin-seeking behaviour in rats. In the present study, we aimed at investigating whether the previously observed cross-talk between cannabinoids and opioids could be extended to mechanisms underlying relapse to cannabinoid-seeking behaviour after a prolonged period of abstinence. In rats previously trained to intravenously self-administer the synthetic cannabinoid Receptor (CB1) Agonist WIN 55,212-2 (12.5 μg kg−1 inf−1) under a fixed ratio (FR1) schedule of reinforcement, noncontingent nonreinforced intraperitoneal (i.p.) priming injections of the previously self-administered CB1 Agonist (0.25 and 0.5 mg kg−1) as well as heroin (0.5 mg kg−1), but not cocaine (10 mg kg−1), effectively reinstate cannabinoid-seeking behaviour following 3 weeks of extinction. The selective CB1 Receptor antAgonist SR 141716A (0.3 mg kg−1 i.p.) does not reinstate responding when given alone, but completely prevents the cannabinoid-seeking behaviour triggered by WIN 55,212-2 or heroin primings. The nonselective opioid antAgonist naloxone (1 mg kg−1 i.p.) has no effect on operant behaviour per se, but significantly blocks cannabinoid- and heroin-induced reinstatement of cannabinoid-seeking behaviour. These results provide the first evidence of drug-induced reinstatement of cannabinoid-seeking behaviour, and further strengthen previous findings on a cross-talk between the endogenous cannabinoid and opioid systems in relapse mechanisms to drug-seeking. British Journal of Pharmacology (2004) 143, 343–350. doi:10.1038/sj.bjp.0705932

  • intravenous self administration of the cannabinoid CB1 Receptor Agonist win 55 212 2 in rats
    Psychopharmacology, 2001
    Co-Authors: Liana Fattore, G Cossu, Cristina M Martellotta, Walter Fratta
    Abstract:

    Rationale: Δ9-Tetrahydrocannabinol (Δ9-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB1) Receptor Agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluating abuse liability of drugs in experimental animals. We recently reported, however, that the synthetic CB1 Receptor Agonist WIN 55,212-2 is intravenously self-administered by drug-naive mice and that its self-administration is blocked by the cannabinoid CB1 Receptor antAgonist SR 141716A. Objective: To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 µg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB1 Receptor antAgonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated. Results: Response rate depended on the drug dose available, with maximum rates occurring at 12.5 µg/kg per injection. Response rate increased following pretreatment with the specific CB1 Receptor antAgonist, SR 141716A. Moreover, operant behaviour rapidly extinguished following both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps. Conclusion: Rats will intravenously self-administer the synthetic CB1 Receptor Agonist WIN 55,212-2 under specific experimental conditions, thus allowing further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour.

Boris B. Gorzalka - One of the best experts on this subject based on the ideXlab platform.

  • suppression of amygdalar endocannabinoid signaling by stress contributes to activation of the hypothalamic pituitary adrenal axis
    Neuropsychopharmacology, 2009
    Co-Authors: Matthew N Hill, Anna C. Morrish, Cecilia J. Hillard, Ryan J Mclaughlin, Victor Viau, Stan B Floresco, Boris B. Gorzalka
    Abstract:

    Endocannabinoids inhibit hypothalamic–pituitary–adrenal (HPA) axis activity; however, the neural substrates and pathways subserving this effect are not well characterized. The amygdala is a forebrain structure that provides excitatory drive to the HPA axis under conditions of stress. The aim of this study was to determine the contribution of endocannabinoid signaling within distinct amygdalar nuclei to activation of the HPA axis in response to psychological stress. Exposure of rats to 30-min restraint stress increased the hydrolytic activity of fatty acid amide hydrolase (FAAH) and concurrently decreased content of the endocannabinoid/CB1 Receptor ligand N-arachidonylethanolamine (anandamide; AEA) throughout the amygdala. In stressed rats, AEA content in the amygdala was inversely correlated with serum corticosterone concentrations. Pharmacological inhibition of FAAH activity within the basolateral amygdala complex (BLA) attenuated stress-induced corticosterone secretion; this effect was blocked by co-administration of the CB1 Receptor antAgonist AM251, suggesting that stress-induced decreases in CB1 Receptor activation by AEA contribute to activation of the neuroendocrine stress response. Local administration into the BLA of a CB1 Receptor Agonist significantly reduced stress-induced corticosterone secretion, whereas administration of a CB1 Receptor antAgonist increased corticosterone secretion. Taken together, these findings suggest that the degree to which stressful stimuli reduce amygdalar AEA/CB1 Receptor signaling contributes to the magnitude of the HPA response.

  • Protracted cannabinoid administration elicits antidepressant behavioral responses in rats: role of gender and noradrenergic transmission.
    Physiology & Behavior, 2009
    Co-Authors: Anna C. Morrish, Matthew N Hill, Caitlin Riebe, Boris B. Gorzalka
    Abstract:

    Abstract Research has shown that enhancement of cannabinoid CB1 Receptor activity elicits an antidepressant-like response in the forced swim test (FST); however, the effects of chronic administration of cannabinoid agents in the FST are not well characterized. In Experiment 1, the CB1 Receptor Agonist HU-210 (0.1 mg/kg) was administered for 10 days to male rats, following which animals were exposed to the FST. In Experiment 2, the same protocol was utilized; however, prior to the FST animals were co-treated with either prazosin (1 mg/kg; an α1-adrenoReceptor antAgonist) or propranolol (2.5 mg/kg; a β-adrenoReceptor antAgonist). In Experiment 3, the same protocol was employed in both male and female rats, and the role of drug withdrawal was examined by administration of the CB1 Receptor antAgonist AM251 (1 mg/kg) prior to the FST. Experiment 1 revealed that HU-210 administration evoked a reduction in immobility and increase in struggling that was identical to that produced by the antidepressant desipramine (10 mg/kg). Experiment 2 revealed that this effect was attenuated by both α- and β-adrenoReceptor antAgonists, suggesting noradrenergic involvement in this antidepressant-like profile. Experiment 3 demonstrated that HU-210 administration produced an antidepressant response in both males and females, which was attenuated by the induction of precipitated withdrawal. These results show that protracted administration of a CB1 Receptor Agonist produces an antidepressant-like response in the FST in both sexes, which appears to involve the noradrenergic system.

  • pharmacological enhancement of cannabinoid CB1 Receptor activity elicits an antidepressant like response in the rat forced swim test
    European Neuropsychopharmacology, 2005
    Co-Authors: Matthew N Hill, Boris B. Gorzalka
    Abstract:

    These experiments aimed to assess whether enhanced activity at the cannabinoid CB1 Receptor elicits antidepressant-like effects. To examine this we administered 1 and 5 mg/kg doses of the endocannabinoid uptake inhibitor AM404; 5 and 25 μg/kg doses of HU-210, a potent CB1 Receptor Agonist; 1, 2.5 and 5 mg/kg of oleamide, which elicits cannabinoidergic actions; 1 and 5 mg/kg doses of AM 251, a selective CB1 Receptor antAgonist, as well as 10 mg/kg desipramine (a positive antidepressant control) and measured the duration of immobility, during a 5-min test session of the rat Porsolt forced swim test. Results demonstrated that administration of desipramine reduced immobility duration by about 50% and that all of AM404, oleamide and HU-210 administration induced comparable decreases in immobility that were blocked by pretreatment with AM 251. Administration of the antAgonist AM 251 alone had no effect on immobility at either dose. These data suggest that enhancement of CB1 Receptor signaling results in antidepressant effects in the forced swim test similar to that seen following conventional antidepressant administration.

  • Pharmacological enhancement of cannabinoid CB1 Receptor activity elicits an antidepressant-like response in the rat forced swim test
    European Neuropsychopharmacology, 2005
    Co-Authors: Matthew N Hill, Boris B. Gorzalka
    Abstract:

    These experiments aimed to assess whether enhanced activity at the cannabinoid CB1 Receptor elicits antidepressant-like effects. To examine this we administered 1 and 5 mg/kg doses of the endocannabinoid uptake inhibitor AM404; 5 and 25 μg/kg doses of HU-210, a potent CB1 Receptor Agonist; 1, 2.5 and 5 mg/kg of oleamide, which elicits cannabinoidergic actions; 1 and 5 mg/kg doses of AM 251, a selective CB1 Receptor antAgonist, as well as 10 mg/kg desipramine (a positive antidepressant control) and measured the duration of immobility, during a 5-min test session of the rat Porsolt forced swim test. Results demonstrated that administration of desipramine reduced immobility duration by about 50% and that all of AM404, oleamide and HU-210 administration induced comparable decreases in immobility that were blocked by pretreatment with AM 251. Administration of the antAgonist AM 251 alone had no effect on immobility at either dose. These data suggest that enhancement of CB1 Receptor signaling results in antidepressant effects in the forced swim test similar to that seen following conventional antidepressant administration. © 2005 Elsevier B.V. and ECNP. All rights reserved.

  • enhancement of anxiety like responsiveness to the cannabinoid CB1 Receptor Agonist hu 210 following chronic stress
    European Journal of Pharmacology, 2004
    Co-Authors: Matthew N Hill, Boris B. Gorzalka
    Abstract:

    Abstract The effect that chronic unpredictable stress had on the anxiety-like response elicited by the cannabinoid Receptor Agonist HU-210 [3-(1,1-dimethylheptyl)-(-)-11-hydroxy-delta8-tetrahydrocannabinol] in the elevated plus maze was investigated here. Male Long–Evans rats were either unstressed or were subjected to a 21-day regimen of chronic unpredictable stress, and subsequently were subdivided into three testing groups (vehicle, 10 and 50 μg/kg of HU-210) and tested on the elevated plus maze. Results demonstrated that in unstressed animals, a low dose of HU-210 induced an anxiolytic response, whereas a high dose induced an anxiogenic response. Further, in stressed animals both the low and the high doses of HU-210 induced anxiogenic responses. These findings suggest that chronic stress enhances either cannabinoid Receptor responsivity or one of the interacting systems implicated in emotional states.

Ferdinando Nicoletti - One of the best experts on this subject based on the ideXlab platform.

  • wag rij rats show a reduced expression of CB1 Receptors in thalamic nuclei and respond to the CB1 Receptor Agonist r win55 212 2 with a reduced incidence of spike wave discharges
    Epilepsia, 2010
    Co-Authors: Clementina M. Van Rijn, Vincenzo Cuomo, Silvana Gaetani, Ines Santolini, Aleksandra Badura, Aleksandra Gabova, Jin Fu, Masashiko Watanabe, Gilles Van Luijtelaar, Ferdinando Nicoletti
    Abstract:

    Purpose: Genetically epileptic WAG/Rij rats develop spontaneous absence-like seizures after 3 months of age. We used WAG/Rij rats to examine whether absence seizures are associated with changes in the expression of type-1 cannabinoid (CB1) Receptors. Methods: Receptor expression was examined by in situ hybridization and western blot analysis in various brain regions of “presymptomatic” 2-month old and “symptomatic” 8-month-old WAG/Rij rats relative to age-matched nonepileptic control rats. Furthermore, we examined whether pharmacologic activation of CB1 Receptor affects absence seizures. We recorded spontaneous spike-wave discharges (SWDs) in 8-month old WAG/Rij rats systemically injected with the potent CB1 Receptor Agonist, R(+)WIN55,212-2 (3–12 mg/kg, s.c.), given alone or combined with the CB1 Receptor antAgonist/inverse Agonist, AM251 (12 mg/kg, s.c.). Results: Data showed a reduction of CB1 Receptor mRNA and protein levels in the reticular thalamic nucleus, and a reduction in CB1 Receptor protein levels in ventral basal thalamic nuclei of 8-month-old WAG/Rij rats, as compared with age-matched ACI control rats. In vivo, R(+)WIN55,212-2 caused a dose-dependent reduction in the frequency of SWDs in the first 3 h after the injection. This was followed by a late increase in the mean SWD duration, which suggests a biphasic modulation of SWDs by CB1 Receptor Agonists. Both effects were reversed or attenuated when R(+)WIN55,212-2 was combined with AM251. Discussion: These data indicate that the development of absence seizures is associated with plastic modifications of CB1 Receptors within the thalamic-cortical-thalamic network, and raise the interesting possibility that CB1 Receptors are targeted by novel antiabsence drugs.

  • WAG/Rij rats show a reduced expression of CB1 Receptors in thalamic nuclei and respond to the CB1 Receptor Agonist, R(+)WIN55,212-2, with a reduced incidence of spike-wave discharges
    Epilepsia, 2010
    Co-Authors: Clementina M. Van Rijn, Vincenzo Cuomo, Silvana Gaetani, Ines Santolini, Aleksandra Badura, Aleksandra Gabova, Jin Fu, Masashiko Watanabe, Gilles Van Luijtelaar, Ferdinando Nicoletti
    Abstract:

    Purpose: Genetically epileptic WAG/Rij rats develop spontaneous absence-like seizures after 3 months of age. We used WAG/Rij rats to examine whether absence seizures are associated with changes in the expression of type-1 cannabinoid (CB1) Receptors. Methods: Receptor expression was examined by in situ hybridization and western blot analysis in various brain regions of “presymptomatic” 2-month old and “symptomatic” 8-month-old WAG/Rij rats relative to age-matched nonepileptic control rats. Furthermore, we examined whether pharmacologic activation of CB1 Receptor affects absence seizures. We recorded spontaneous spike-wave discharges (SWDs) in 8-month old WAG/Rij rats systemically injected with the potent CB1 Receptor Agonist, R(+)WIN55,212-2 (3–12 mg/kg, s.c.), given alone or combined with the CB1 Receptor antAgonist/inverse Agonist, AM251 (12 mg/kg, s.c.). Results: Data showed a reduction of CB1 Receptor mRNA and protein levels in the reticular thalamic nucleus, and a reduction in CB1 Receptor protein levels in ventral basal thalamic nuclei of 8-month-old WAG/Rij rats, as compared with age-matched ACI control rats. In vivo, R(+)WIN55,212-2 caused a dose-dependent reduction in the frequency of SWDs in the first 3 h after the injection. This was followed by a late increase in the mean SWD duration, which suggests a biphasic modulation of SWDs by CB1 Receptor Agonists. Both effects were reversed or attenuated when R(+)WIN55,212-2 was combined with AM251. Discussion: These data indicate that the development of absence seizures is associated with plastic modifications of CB1 Receptors within the thalamic-cortical-thalamic network, and raise the interesting possibility that CB1 Receptors are targeted by novel antiabsence drugs.

Nicholas V Dipatrizio - One of the best experts on this subject based on the ideXlab platform.

  • δ9 thc induced hyperphagia and tolerance assessment interactions between the CB1 Receptor Agonist δ9 thc and the CB1 Receptor antAgonist sr 141716 rimonabant in rats
    Behavioural Pharmacology, 2005
    Co-Authors: Torbjorn U C Jarbe, Nicholas V Dipatrizio
    Abstract:

    This study examined effects of the CB1 Receptor antAgonist/inverse Agonist SR-141716 and the CB1 Receptor Agonist Δ9-tetrahydrocannabinol (Δ9-THC) on feeding behavior in male Sprague–Dawley rats. Rats were housed individually with free access to regular pelletized laboratory chow [after a 2 weeks ha

  • adamantyl δ8 tetrahydrocannabinol am 411 a selective cannabinoid CB1 Receptor Agonist effects on open field behaviors and antagonism by sr 141716 in rats
    Behavioural Pharmacology, 2004
    Co-Authors: Torbjorn U C Jarbe, Nicholas V Dipatrizio, Dai Lu, Alexandros Makriyannis
    Abstract:

    (-)-Adamantyl-Δ 8 -tetrahydrocannabinol (AM-411) is a 'classical' tricyclic cannabinoid CB 1 Receptor Agonist in which the C-3 alkyl side-chain has been replaced with an adamantyl group. The compound is cannabinoid CB 1 Receptor subtype selective (CB 1 Ki = 6.86 nmol/l, CB 2 Ki = 52.0 nmol/l). We examined the effects of AM-411 alone and in combination with the cannabinoid CB 1 Receptor antAgonist/inverse Agonist, SR-141716, on open-field behaviors of rats. The lowest effective dose of AM-411, 3 mg/kg, suppressed ambulation (horizontal activity) and rearing (vertical activity) and increased circling frequency compared to vehicle control levels. Co-administration of SR-141716 normalized these changes. SR-141716 (3 and 5.6 mg/kg) also produced significant increases in scratching and grooming (both frequency and duration), effects that were not eliminated in the presence of AM-411. Coupled with previous drug discrimination data, the open-field profile of AM-411 suggests that this high-affinity CB 1 cannabinoid Receptor Agonist induces behavioral effects similar to the natural cannabinoid Δ 9 -tetrahydrocannabinol and different from (R)-methanandamide, a chiral analog of the endogenous ligand anandamide.

  • interactions between the CB1 Receptor Agonist δ9 thc and the CB1 Receptor antAgonist sr 141716 in rats open field revisited
    Pharmacology Biochemistry and Behavior, 2002
    Co-Authors: Torbjorn U C Jarbe, Matthew E Andrzejewski, Nicholas V Dipatrizio
    Abstract:

    Abstract This study examined the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and the CB1 antAgonist SR-141716 on open-field behaviors in male Sprague–Dawley rats. Animals were examined after administration of Δ9-THC alone (dose range: 0.3–5.6 mg/kg), SR-141716 alone (dose range: 1–5.6 mg/kg) and the two drugs in combination; injections were given intraperitoneally 30 min prior to testing. There was a dose-related suppression of ambulation (horizontal activity) and rearing (vertical activity) after Δ9-THC administration. Co-administration of SR-141716 counteracted this suppression; however, antagonism was only partial for rearing. Interestingly, 1 mg/kg SR-141716 was as effective as 3 and 5.6 mg/kg SR-141716 in this antAgonist action. Increasing doses of Δ9-THC produced an increase in circling behavior; latency to leave the starting area in the center of the field was significantly elevated by 5.6 mg/kg Δ9-THC. Those effects were completely blocked by SR-141716. Grooming and scratching showed a dose-related increase following administration of SR-141716 (1–5.6 mg/kg), which were only partially blocked by co-administration of Δ9-THC (3 and 5.6 mg/kg). When given alone, only the highest dose of SR-141716 (5.6 mg/kg) depressed ambulation; rearing and latency were not significantly changed, and circling was absent. Differences in the number of vocalizations, urination and defecation generally did not differ clearly among the treatment conditions. These results may show that SR-141716 is acting as (i) an inverse Agonist and/or (ii) that the endogenous cannabinoid system is tonically active under certain conditions.