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  • 11
    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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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 101 (1990), S. 403-407 
    ISSN: 1432-2072
    Keywords: Serotonin uptake blockers ; Learned helplessness ; Rats ; Depression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serotonergic systems are thought to be involved in the mechanisms of action of antidepressants in humans. There is little evidence, however, to suggest that serotonin uptake blockers are efficacious in animal models of depression. To further explore the antidepressant activity of these drugs, four compounds from this class (citalopram, fluvoxamine, indalpine or zimelidine) were tested in rats subjected to helplessness training. Rats were first exposed to inescapable shocks and 48 h later, shuttle-box training was initiated to evaluate escape learning. Twice-daily IP injections of citalopram (1 mg/kg), fluvoxamine (4 mg/kg), indalpine (1 and 2 mg/kg) and zimelidine (1 and 2 mg/kg) reduced escape deficits in a manner similar to that produced by the tricyclic antidepressants desipramine and clomipramine. Reversal of escape deficit by serotonin uptake blockers was observed only when the drugs were administered after the shuttle-box sessions. At higher doses, the four serotonin uptake blockers were without effect. These data suggest that serotonin uptake blockers exert antidepressant-like effects in animals but only when they produce a moderate stimulation of serotonin neurotransmission.
    Type of Medium: Electronic Resource
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  • 13
    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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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 86 (1985), S. 147-152 
    ISSN: 1432-2072
    Keywords: Benzodizepines ; Indalpine ; Zimelidine ; Serotonergic neurons ; Waiting capacity ; Impulse control ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated whether benzodiazepines reduce the capacity of animals to wait for food reward. Rats trained in a T-maze were allowed to choose between two magnitudes of reward: immediate, but small (two pellets) vs delayed, but large (eight pellets). The rats learned within ten sessions to select (80–100%) the arm leading to the largest reward. Separate groups of rats were then confined for 15, 30 or 60 s in the arm associated with the largest reward before gaining access to the spacially contiguous goal-box. The choice of the other arm was not followed by a period of waiting. Under these conditions, the frequency with which the small-reward arm was chosen increased linearly as a function of the duration of the waiting period. Diazepam (2–4 mg/kg IP) dose-dependently increased the number of times the small-reward arm was chosen during the sessions for which the waiting period was fixed at 15 or 30 s. Nitrazepam (2 mg/kg IP), chlordiazepoxide (16 mg/kg IP) and clobazam (16 mg/kg IP) had similar effects. The action of diazepam was counteracted by simultaneous administration of flumazepil (Ro 15-1788, 8 mg/kg PO). In the absence of confinement, these benzodiazepines, diazepam (4 mg/kg) excepted, did not modify selection of the large-reward arm. Conversely, the serotonin uptake blockers indalpine (2–4 mg/kg IP) and zimelidine (8–16 mg/kg IP) dose-dependently increased preference for the arm leading to the delayed (25 s) but large reward. These results suggest that benzodiazepines, perhaps by increasing impulsivity, render the animals less prone than controls to tolerate delayed access to reward. It is hypothesized that serotonergic neurons play a crucial role in impulse control and in the benzodiazepines-induced shift towards the immediate reward.
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  • 15
    ISSN: 1432-2072
    Keywords: Duration of punishment ; Delay of reward ; Behavioral suppression ; Benzodiazepines ; Diazepam ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study investigated in rats whether variables which may affect the animals' tolerance for delay of reward could be critical for the benzodiazepine-induced release of punished behavior. Rats were subjected to conflict situations during which signalled FR4 non-punished periods (lights-off) alternated with punished periods of different durations signalled by lights-on stimuli. Lever presses during punished periods resulted in the delivery of both one food-pellet and one electric foot-shock (0.45 mA). The antipunishment effect of diazepam (2 mg/kg IP) clearly depended on the duration of the punished periods, release of punished behavior being observed only when punished periods exceeded 1 min. The duration of punished periods required for diazepam-induced release of responding was affected by factors which modified the contrast between rewards received in punished and non-punished periods. One of these factors was the FR schedule imposed during non-punished periods, since the anti-punishment effect of diazepam was observed during short-lasting (30-s and 1-min) punished periods separated by FR24 non-punished periods. A second factor was the ratio of the durations of punished and non-punished periods: diazepam released behavior during 2-min punisheds when the duration of the intercurrent non-punished periods was 1 min, but not when it was 4 min. The predictability of the duration of the punished periods also modulated the effect of diazepam since: with 1 min punished periods, diazepam released punished responding during the first exposures of the rats to the experimental session, but lost part or all its efficacy in animals extensively trained to the procedure. It is tentatively proposed that not only punishment, but also delay of reward induced by passive avoidance of the punished response, are affected by benzodiazepines.
    Type of Medium: Electronic Resource
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  • 16
    ISSN: 1432-2072
    Keywords: SR 46559A ; Cholinergic syndrome ; Memory ; Diacylglycerol ; Muscarinic receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cholinergic activities of SR 46559A, 3-[N-(2 diethyl-amino-2-methylpropyl)-6-phenyl-5-propyl] pyridazinamine sesquifumarate, have been investigated in vitro and in vivo, in rodents. Using rat brain cortical membranes, SR 46559A was a competitive ligand (Ki=112 nM) at muscarinic M1 receptors, its affinity for muscarinic M2 (cardiac) and M3 (glandular) receptors being 6–7 times lower. SR 46559A did not interact with brain nicotinic receptors and high affinity choline uptake sites nor did it inhibit brain acetylcholinesterase activity. In contrast to reference muscarinic agonists, SR 46559A (1 mM) did not inhibit the forskolin-induced activation of cAMP synthesis nor did it stimulate phosphoinositides breakdown in various brain preparations. However, this compound enhanced (+67% at 1 mM) diacylglycerol formation in rat striatal miniprisms, an effect fully reversed by atropine. As shown with reference agonists, SR 46559A inhibited (IC50=10 µM) the K+-evoked release of [3H]GABA from rat striatal slices and reduced at 0.5 and 1 µM, the population spike amplitude of the CA1 pyramidal cells induced by stimulation of the Schaffer's collateral commissural pathway in rat hippocampal slices. In mice, SR 46559A at a near lethal dose (200 mg/kg PO) did not induce the typical cholinergic syndrome nor did it modify at 30 mg/kg PO the oxotremorine-induced hypothermia. Like muscarinic agonists, SR 46559A (1 mg/kg PO) potentiated haloperidol-induced catalepsy in rats and inhibited (ED50=0.12 mg/kg PO) rotations induced in mice by intrastriatal injection of pirenzepine. SR 46559A prevented the scopolamine- or pirenzepine-induced deficit in passive avoidance learning, this compound being 3 times more potent on pirenzepine-induced amnesia. Moreover, using the social memory test, SR 46559A (0.1–3 mg/kg PO) enhanced short-term retention in adult rats and improved memory deficits observed in aged mice and in rats subjected to cerebral ischeamic insult. SR 46559A (1–3 mg/kg PO) also reversed the ischaemia-induced alterations of rats exploratory behaviour. Taken together, these results suggest that SR 46559A behaves as an atypical muscarinic compound which, at least in part, could stimulate muscarinic receptors coupled to phosphatidylcholine/phospholipases C or D signalling pathways. This drug has a marked ability to improve experimentally induced cognitive deficits in rodents without producing cholinergic symptomatology. Thus, SR 46559A could be a potential useful drug for the symptomatic treatment of Alzheimer's disease.
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