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  • 5-HT receptor subtypes  (1)
  • 7-dihydroxytryptamine  (1)
  • 1
    ISSN: 1432-2072
    Keywords: Dexfenfluramine ; 5-HT receptor subtypes ; Tolerance ; Heroin self-administration ; Rat ; Metergoline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present series of experiments sought to investigate further the mechanism by which dexfenfluramine, a selective 5-HT releaser/reuptake inhibitor, reduces heroin self-administration by male Wistar rats. In experiment 1, the effect of combined intravenous heroin and intraperitoneal dexfenfluramine injections on operant responding for food was examined. In experiment 2, the maintenance of dexfenfluramine suppression of heroin self-administration following chronic (7 day) treatment was evaluated. Finally, in experiment 3, the ability of various 5-HT antagonists to block the dexfenfluramine suppression was examined. The results from experiment 1 suggest that sensorimotor deficits/malaise potentially associated with heroin/dexfenfluramine combinations are unlikely to account for the reductions in heroin self-administration. Experiment 2 suggested that the suppressant effect of dexfenfluramine on heroin responding may diminish rapidly following chronic treatment. Finally, central 5-HT1 and/or 5-HT2, but not 5-HT3, receptors may underlie the suppressant effects of dexfenfluramine on heroin self-administration.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Serotonin ; 5 ; 7-dihydroxytryptamine ; Conditioned reward ; Amphetamine ; Nucleus accumbens ; Motivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Previously, we have shown that increasing 5-hydroxytryptamine (5-HT) activity attenuates responding for conditioned reward (CR), and the response potentiating effect of d-amphetamine on this behaviour. Objectives: The present experiments examined the effects of reducing 5-HT function on responding for CR. Methods: In experiment 1, thirsty rats were trained to associate a CS+ with water delivery. The neurotoxin 5,7-DHT was then injected into the dorsal and median raphe nuclei. Subsequently, rats were treated with intra-accumbens d-amphetamine (1, 3, 10 µg) or saline and given access to two levers. One lever delivered the CS+ (now termed a CR), while the other was inactive. In experiment 2, the lesion was carried out prior to conditioning, and approach behaviour to the water magazine was measured during CS+ periods. Subsequently, rats were allowed to respond for the CS. In experiment 3, non-deprived rats learned to associate a CS+ with 10% sucrose; these animals also experienced a CS– which was not paired with sucrose. During a test phase responses on the two levers delivered either the CS+ or the CS–. Results: 5,7-DHT substantially reduced 5-HT levels in striatum and hippocampus. In experiment 1, responding for the CR was enhanced by both d-amphetamine and 5-HT depletion in an additive fashion. In experiments 2 and 3, the discriminative control over behaviour exerted by the CS+ was not affected by 5-HT depletion. However, compared to control animals 5-HT-depleted rats showed higher levels of operant responding for the CR. Conclusions: Serotonin depletion selectively enhances responding for CR. Although 5-HT depletion did not potentiate the effects of d-amphetamine, it is suggested that CRs activate the mesolimbic dopamine system, and that removal of an inhibitory influence of 5-HT on the activity of this system results in increased responding for CR in 5,7-DHT-treated rats.
    Type of Medium: Electronic Resource
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