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  • d-Amphetamine  (3)
  • 5-HT receptor subtypes  (1)
  • 1
    ISSN: 1432-2072
    Keywords: Conditioned reward ; d-Fenfluramine ; d-Amphetamine ; Metergoline ; Nucleus accumbens ; 5-Hydroxytryptamine dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These studies investigated the effects of the 5-hydroxytryptamine (5-HT) releaser, and re-uptake inhibitor,d-fenfluramine, and the non-selective 5-HT receptor antagonist metergoline, on responding for conditioned reward (CR), and on the potentiation of responding for CR following amphetamine injected into the nucleus accumbens. Water deprived rats were trained to associate a compound stimulus with water delivery during a conditioning phase. During a test phase, water was not delivered but the compound stimulus was delivered according to a random ratio 2 schedule following a response on one of two levers; responding on the other lever was not reinforced. Overall, rats responded at a higher rate on the lever delivering the CR.d-Amphetamine (1, 3 and 10 µg) injected into the nucleus accumbens dose-dependently enhanced responding on the CR lever. Treatment withd-fenfluramine (0.5 and 1 mg/kg) reduced responding for the CR, and abolished the potentiating effect ofd-amphetamine. Responding on the inactive lever was also reduced by 1 mg/kg but not 0.5 mg/kgd-fenfluramine. The reduction ofd-amphetamine's effect on responding for CR was prevented by prior treatment with the 5-HT receptor antagonist metergoline (1 mg/kg). Control experiments showed that changes in thirst and motor performance, as well as deficits in learning ability, cannot account for the effects ofd-fenfluramine in this paradigm. In a separate experiment, 1 mg/kg metergoline failed to enhance responding for CR, and to augment the response potentiating effect of a low dose (2 µg) ofd-amphetamine injected into the nucleus accumbens. Thus, elevating brain 5-HT activity appears to reduce the ability of secondary reinforcing stimuli to elicit and maintain behaviour, and antagonizes the effects of enhanced dopamine activity within the nucleus accumbens. However, reduced 5-HT function induced by blockade of 5-HT1/2 receptors does not appear to influence responding for CR, or the response potentiating effect ofd-amphetamine. These results suggest that 5-HT may play an important role in mediating incentive motivation.
    Type of Medium: Electronic Resource
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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 126 (1996), S. 62-69 
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; Nucleus accumbens ; d-Amphetamine ; Conditioned reward ; Dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Injection ofd-amphetamine into the nucleus accumbens potentiates responding for stimuli paired with a primary reward. A previous study showed that this potentiating effect ofd-amphetamine on responding for conditioned reward (CR) was attenuated by peripherally injectedd-fenfluramine, a 5-hydroxytryptamine (5-HT) releaser and re-uptake inhibitor. The present experiments further examined the effects of manipulating 5-HT function within the nucleus accumbens on responding for CR, and on the potentiation of CR responding following intra-accumbens injection ofd-amphetamine. Water deprived rats were trained to associate a compound stimulus with water delivery during a conditioning phase. During a test phase water was not delivered, but the compound stimulus was delivered according to a random ratio 2 schedule following a response on one of two levers. Rats responded at a higher rate on the lever delivering this CR.d-Amphetamine (10 μg) injected into the nucleus accumbens enhanced responding on the CR lever. Co-injections of 5-HT (5 and 10 μg) into the nucleus accumbens abolished the response-potentiating effect ofd-amphetamine but were without effect on the base-line level of responding for CR. This reduction by 5-HT of the response potentiating effect ofd-amphetamine was prevented by prior treatment with the 5-HT receptor antagonist metergoline (1 mg/kg). Responding for water was not altered by 5-HT and so the effects of 5-HT on responding for CR cannot be due to a change in the motivation to seek the primary reward. Thus, elevating 5-HT activity within the nucleus accumbens antagonises the effects ofd-amphetamine on responding for CR within the nucleus accumbens. These results suggest that 5-HT within the nucleus accumbens may play an important role in mediating incentive motivation by modulating dopaminergic neurotransmission.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 134 (1997), S. 64-72 
    ISSN: 1432-2072
    Keywords: Key words Ondansetron ; d-Amphetamine ; α-Flupenthixol ; Nucleus accumbens ; Conditioned reward
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous experiments have suggested that 5-HT3 antagonists such as ondansetron may alter reward-related behaviour that is dependent in part upon raised mesolimbic dopamine activity. However, the evidence for this is far from conclusive. One major behavioural role of dopamine is in the control of behaviour elicited by conditioned rewarding stimuli. To date, the effects of 5-HT3 antagonists on this function of mesolimbic dopamine have not been examined. Two experimental procedures were employed to examine the effects of ondansetron (10 and 100 μg/kg) on the acquisition of responding for conditioned reward, and on the response potentiating effect of intra-accumbens d-amphetamine (10 μg). These effects were compared to those elicited by the dopamine antagonist α-flupenthixol (0.1 mg/kg). In the first procedure, rats were trained to associate food pellet delivery with a conditioned stimulus (CS). Rats subsequently allowed to respond on a lever delivering this CS, and on an inactive lever, showed a greater preference for the lever delivering the CS, indicating that this CS functioned as a conditioned reward (CR). Ondansetron administered during the conditioning phase did not alter subsequent responding for the CR, but α-flupenthixol induced a small but significant reduction in responding on the CR lever. These results suggest that blockade of dopamine receptors, but not 5-HT3 receptors interfere with the learning of stimulus reward relationships. In the second procedure, d-amphetamine injected into the nucleus accumbens markedly potentiated responding for CR. Ondansetron at 10 μg/kg induced a small attenuation of this effect, without altering responding in its own right. However, at a higher dose (100 μg/kg) ondansetron plus amphetamine treatment significantly enhanced responding on the inactive lever. At both doses, the net effect of ondansetron was to produce a subtle impairment in the allocation of responses such that the differential responding on the CR versus NCR lever was diminished. In contrast to these effects α-flupenthixol significantly attenuated d-amphetamine’s selective enhancement of responding for conditioned reward, as well as impairing the ability of the conditioned reward to elicit and maintain behaviour. These results confirm the role of dopamine in responding for conditioned reward, and suggest a possible modulators role for 5-HT3 receptors in this process. However, the effects of ondansetron on the acquisition of, and responding for, conditioned reward are clearly different from those induced by blockade of dopamine receptors.
    Type of Medium: Electronic Resource
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