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  • 1
    ISSN: 1432-1912
    Keywords: Key words Hippocampal slice ; Long-term potentiation ; CB1 receptors ; Anandamide ; WIN55212-2 ; SR141716 A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It has been reported previously that Δ9-tetrahydrocannabinol and the synthetic cannabinoid agonist HU-210 [(−)-11-OH-Δ8-dimethylheptyl tetrahydrocannabinol] prevent long-term potentiation (LTP) induction in rat hippocampal slices. In this study we confirm that both WIN55212-2 {R-(+)-(2,3-dihydro-5-methyl-3-[{4-morpholinyl} methyl] pyrol[1, 2, 3-de]-1,4-benzoxazin-6-yl) (1-naphtalenyl) methanone monomethanesulphonate} (3 and 10 μM), another synthetic cannabinoid agonist, and anandamide (10 μM), considered to be the endogenous ligand of cannabinoid receptors, inhibit LTP formation in the Schaffer collateral-CA1 field complex. In addition, we show that SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] at 0.1–10 μM, a potent and selective antagonist of CB1 cannabinoid receptors, concentration-dependently reversed the inhibition of LTP induced by both WIN55212-2 and anandamide. These data indicate that cannabinoid receptor agonists inhibit hippocampal LTP formation through CB1 receptor activation and that anandamide could be a candidate for an endogenous neuromessenger involved in memory processes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Hippocampal slice ; Long-term potentiation ; CB1 receptors ; Anandamide ; WIN55212-2 ; SR141716 A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been reported previously that Δ9-tetrahydrocannabinol and the synthetic cannabinoid agonist HU-210 [(−)-11-OH-Δ8-dimethylheptyl tetrahydrocannabinol] prevent long-term potentiation (LTP) induction in rat hippocampal slices. In this study we confirm that both WIN55212-2 {R-(+)-(2,3-dihydro-5-methyl-3-[{4-morpholinyl} methyl] pyrol [1,2,3-de]-1,4-benzoxazin-6-yl) (1-naphtalenyl) methanone monomethanesulphonate} (3 and 10 μM), another synthetic cannabinoid agonist, and anandamide (10 μM), considered to be the endogenous ligand of cannabinoid receptors, inhibit LTP formation in the Schaffer collateral-CA1 field complex. In addition, we show that SRt417l6A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-lH-pyrazole-3-carboxamide hydrochloride] at 0.1–10 μM, a potent and selective antagonist of CB1 cannabinoid receptors, concentration-dependently reversed the inhibition of LTP induced by both WIN55212-2 and anandamide. These data indicate that cannabinoid receptor agonists inhibit hippocampal LTP formation through CB1 receptor activation and that anandamide could be a candidate for an endogenous neuromessenger involved in memory processes.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Sucrose intake ; Ethanol consumption ; Cannabinoid receptor ; SR 141716 ; Rats ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract SR 141716, a selective central CB1 cannabinoid receptor antagonist, markedly and selectively reduces sucrose feeding and drinking as well as neuropeptide Y-induced sucrose drinking in rats. SR 141716 also decreases ethanol consumption in C57BL/6 mice. In contrast, blockade of CB1 receptors only marginally affects regular chow intake or water drinking. The active doses of SR 141716 (0.3–3 mg/kg) are in the range known to antagonize the characteristic effects induced by cannabinoid receptor agonists. These results suggest for the first time that endogenous cannabinoid systems may modulate the appetitive value of sucrose and ethanol, perhaps by affecting the activity of brain reward systems.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Key words Cannabinoid receptors ; Cocaine ; Food ; Incentive learning ; Morphine ; Rat ; Reward ; SR 141716 ; WIN 55212-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The involvement of cannabinoid processes in positive reinforcement was studied using an unbiased, one-compartment, conditioned place preference (CPP) procedure in rats. This was achieved by examining the ability of the selective antagonist of the CB1 cannabinoid receptor subtype, SR 141716, to counteract the CPP supported by classical reinforcers. The acquisition of CPP induced by cocaine (2 mg/kg), morphine (4 mg/kg) and food (standard chow and sucrose pellets) was dose-dependently blocked by pre-pairing administration of SR 141716 (0.03–3 mg/kg). However, SR 141716 (up to 10 mg/kg) did not significantly counteract the expression of cocaine-induced CPP. On the other hand, the synthetic CB receptor agonist, WIN 55212-2 (0.3–1 mg/kg), established a robust place aversion (CPA), as already described with other agonists, and CPP was never observed, even at 100-fold lower doses. The aversive effect of WIN 55212-2 was reversed by SR 141716 (0.3–1 mg/kg), suggesting that it was accounted for by the stimulation of CB1 receptors. These findings indicate that, on their own, CB receptor agonists are unable to generate the processes necessary to induce a pleasurable state in animals, as assessed in place conditioning procedures. Nevertheless, a cannabinoid link may be involved in the neurobiological events, allowing the perception of the rewarding value of various kinds of reinforcers. However, a permanent endogenous cannabinoid tone seems unlikely to be necessary to ensure the organism a basal hedonic level since, given alone, SR 141716 supported neither CPP nor CPA.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Key words Cannabinoid receptor ; Locomotor activity ; Habituation ; Antipsychotic drug ; Gerbils
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: A cannabinoid hypothesis of schi- zophrenia has been proposed according to which cognitive dysfunction could be associated with dysregulation of an endogenous cannabinoid system. Objective: The present study investigated whether SR 141716, a selective CB1 receptor antagonist, was able to reduce the hyperactivity induced in gerbils by various stimulant drugs known to produce or exacerbate schizophrenic symptoms. Methods: Cocaine, d-amphetamine, morphine, and Win 55212-2 were administered intraperitoneally (IP) either immediately before placing the animals in the test apparatus (non-habituated gerbils) or after a 2- to 3-h habituation period in the actimeter (habituated gerbils). SR 141716 was given IP 30 min before the injection of stimulant drugs. Horizontal activity was recorded every 10 min for 1 h in Digiscan activity monitor. Results: SR 141716 (0.3–3 mg/kg) dose-dependently suppressed the enhanced locomotor activity induced by each stimulant drug in habituated gerbils, but not in non-habituated animals. Clozapine, an atypical antipsychotic compound, but not haloperidol, shared with SR 141716, the ability to differentially affect drug-induced hyperactivity in habituated versus non-habituated gerbils. Conclusion: The activation of cannabinoid systems is a required, permissive element in the ability of cocaine, d-amphetamine, morphine, and Win 55212-2 to reinstate behaviour, i.e., to override stimulus satiation.
    Type of Medium: Electronic Resource
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