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Effect of fipexide on passive avoidance behaviour in rats
No full textThe effect of fipexide, administered at different intervals after the learning trial of a single step-through type passive avoidance situation was studied. The administration of fipexide immediately after the learning trial resulted in a long-lasting facilitation of passive avoidance behaviour. On the contrary, the administration of this compound 1 h prior to the retention test failed to influence passive avoidance behaviour. The results suggest that fipexide facilitates memory consolidation but does not influence retrieval processes
Dopamine and opioids interactions in sleep deprivation
No full text1. Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 hrs) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity,increased alertness and reactivity to enviromental stimuli. 2. Our results indicate that this behavior is potently antagonized by the administration of D1 antagonist SCH 23390 and by the opioid antagonist naloxone. 3. We also show that concomitantly to this behavior, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. On the contrary, a decreased Bmax of mu and delta opioid receptors was found in the same brain areas. 4. These data suggest an active role of limbic dopamine and opioid system in the generation of arousal and insomnia related to sleep deprivation-induced stress
Dopamine D1 and opioid receptor binding changes in the limbic system of sleep deprived rats
No full textSleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behavior was potently antagonized by the administration of the D1 selective antagonist SCH 23390 and by the opioid antagonist naloxone. In this paper we show that concomitantly to this behavior, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. On the contrary, a decreased Bmax of mu and delta opioid receptors was found in the same brain area. These data suggest an active role of limbic dopamine and opioid systems in the generation of arousal and insomnia related to sleep deprivation-induced stress
Rewarding properties of gamma-hydroxybutyric acid: an evaluation trouth place preference paradigm
No full textGamma-hydroxybutyric acid (GHB), a putative neurotransmitter or neuromodulator found in the mammalian brain, has been successfully used in clinical practice to alleviate both alcohol and opiate withdrawal symptoms. In the present study we used a conditioned place preference (CPP) paradigm to investigate whether GHB possesses rewarding properties in rats. In order to exclude possible artifacts due to experimental design, we evaluated the possibility of a shift in preference when rats are conditioned either on their non-preferred side or on a randomly assigned side of conditioning. In both experiments GHB was seen to induce CPP. Although to date the physiological role of this compound still remains unclear, there is no doubt that GHB, further to its proven effect on alcohol and opiates, possesses rewarding properties of its own. The abuse liability afforded by this drug suggests the use of particular caution in handling GHB as a clinically useful drug
Intravenous self-administration of gamma-hydroxybutyric acid in drug-naive mice
No full textThe reinforcing effects of gamma-hydroxybutyric acid (GHB) were studied by means of intravenous self-administration in drug-naive mice. GHB self-administration was concentration-dependent (0.01-0.5 mg/kg/inj) according to a bell-shaped curve. Pretreatment with the specific GHB receptor antagonist NCS-382 at a dose of 12.5 mg/kg i.p. completely antagonized the reinforcing effects of GHB. These data suggest that GHB is able to induce reinforcing effects in mice and support the hypothesis of an abuse liability of this drug. (C) 1998 Elsevier Science B.V./ECNP. All rights reserved
Baclofen antagonizes intravenous self-administration of gamma-hydroxybutyric acid in mice
No full textGamma -Hydroxybutyric acid (GHB) is a widely used recreational drug known to exert positive reinforcing effects in animals and humans. The GABAB receptor agonist baclofen has been proved to possess antimotivational effect and to inhibit alcohol, cocaine, heroin and nicotine intake. In the present study we evaluated the effect of baclofen on i.v, self-administration of GHB in drug-naive mice under a fixed-ratio (FR-I) schedule of reinforcement and nose-poking-like response as operandum. Results show that baclofen was able to completely prevent GHB seeking behaviour, decreasing the rate of responding to basal values, without showing any reinforcing properties when made contingent on nose-poking response. Our findings demonstrate that baclofen antagonises GHB i.v. self-administration, supporting an important role for the GABAB receptor in reward-related mechanisms underlying addictive behaviour. NeuroReport 12:2243-2246 (C) 2001 Lippincott Williams & Wilkins
CB1 cannabinoid receptor agonist WIN 55,212-2 decreases intravenous cocaine self-administration in rats
No full textThe effect of the CB, cannabinoid receptor agonist WIN 55, 212-2 on intravenous cocaine self-administration (IVSA) in rats was evaluated. Male Long Evans rats were implanted with silastic catheters through the external jugular vein. The IVSA was conducted in 3-h daily sessions with a fixed ratio (FR1) schedule: the experimental apparatus had a nose-poking response-like operandum. Intravenous pre-treatment with WIN 55, 212-2 (0.25, 0.5 and 1 mg/kg) to rats self-administering cocaine (0.25 or 0.5 mg/kg/inj) at stable baseline, reduces cocaine intake in a dose-dependent manner. The CB, receptor antagonist SR 141716A (3 mg/kg i.p.) completely reversed the WIN 55, 212-2-induced decrease of cocaine intake. However, pre-treatment of SR 141716A alone (up to dose of 9 mg/kg i.p.) was unable to modify cocaine IVSA. These results indicate that stimulation of CB, cannabinoid receptors activates rewarding mechanisms which produce reinforcing effects additional to those induced by cocaine. (C) 1999 Elsevier Science B.V. All rights reserved
Effect of isradipine, a Dihydropyridine-calcium antagonist oni.v. self-administration of morphine in rats
No full textThe effect of dihydropyridine calcium channel antagonist isradipine (PN 200-110) on morphine reinforcement has been investigated using i.v. self-administration test in rats. Rats were given the opportunity to self-administer a solution of morphine (1 mg/ml, i.v.) in a 1 hr limited access paradigm (FR = 1). Within 5-7 days rats had learned to self-administer approximately 1 mg of morphine in 1 hr as evidenced by a plateau of responding. The administration of isradipine (1.2, 2.5 and 5.0 mg/kg s.c.) 90 min before the morphine self-administration session, induced dose-dependent increase in the number of morphine self-infusions with respect to basal values. This response pattern was very similar to the one observed when morphine solution was substituted by saline in trained rats not treated with isradipine. The results indicate that isradipine inhibits partially the reinforcing properties of morphine in self-administration test
The calcium antagonist PN 200-110 inhibits the reinforcing properties of cocaine
No full textThe effect of a dihydropyridine (DHP) calcium antagonist, PN 200-110, on cocaine reinforcing properties was investigated using conditioned place preference paradigm. PN 200-110 in nonsedative doses (0.62-1.25-2.5 mg/kg SC) was able to inhibit cocaine- (10 mg/kg IP) induced place preference with ED50 1.57 (0.88-2.58). The results suggest a possible use of DHPs in the treatment of cocaine-related disorders
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