The effect of a 5-HT3 receptor antagonist, ondansetron, on brain stimulation reward, and its interaction with direct and indirect stimulants of central dopaminergic transmission

Montgomery, A. M. J.; Röse, I; Herberg, L.J.

doi:10.1007/bf01244914

Cited by 28 publications

(4 citation statements)

References 31 publications

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“…Our results are also in agreement with others who report a lack of effect with 5-HT3 receptor antagonists on the reversal of threshold shifts in ICSS tasks induced by amphetamine or nicotine (Montgomery, Rose and Herberg, 1993). Neverthelesss there may be circumstances under which 5-HT3 receptors do play a role.…”

Section: Discussionsupporting

confidence: 93%

The 5 -HT3 receptor antagonists, granisetron and ondansetron, do not affect cocaine-induced shifts in intra-cranial self-stimulation thresholds

1995

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The effects of the 5-HT( 3) receptor antagonists, granisetron and ondansetron, were investigated on behaviour maintained by intracranial self-stimulation (ICSS). Rats, implanted with bipolar electrodes in the lateral hypothalamus, were trained to lever press on a continuous reinforcement schedule for positively reinforcing trains of electrical stimulation. The frequency at which responding reached 50% of maximum (M50) and the maximum rate of responding (asymptote) were used to measure drug effects. Granisetron (0.01-0.1 mg/kg i.p ) and ondansetron (0.03-0.3 mg/kg i.p ) had no effect on either parameter. In contrast, cocaine (20 mg/kg i.p ) potentiated rewarded responding, reducing M50 values, but neither granisetron (0.01-3.0 mg/kg i.p ) nor ondansetron (0.03-0.3 mg/kg i.p ) blocked this effect. Neither did granisetron (0.1-10.0 mg/kg i.p ) alter the effect of lower doses of cocaine (10 mg/kg i.p.). These data suggest that 5 -HT( 3) receptors do not play a significant role in mediating responding maintained by ICSS in the rat through hypothalamic electrodes. Neither do they modulate cocaine-induced potentiation of the behaviour.

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Section: Discussionsupporting

confidence: 93%

The 5 -HT3 receptor antagonists, granisetron and ondansetron, do not affect cocaine-induced shifts in intra-cranial self-stimulation thresholds

1995

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“…5HT3 receptors are abundant in central DA terminal areas, such as the NAc and striatum, and appear to mediate the excitatory effect of compounds acting upstream from DA neurons. 173 Altering 5HT3 transmission with the 5HT3 antagonist ondansetron inhibits cocaine-induced sensitization, 174 decreases alcohol use in early-onset alcohol-dependent subjects, 175 and is being evaluated in phase II clinical trials for cocaine dependence. 176 Cannabinoids activate mesolimbic DA through the CB1 receptor, and the CB1 receptor antagonist rimonabant decreases cocaine reinstatement.…”

Section: Future Directions: Medication Developmentmentioning

confidence: 99%

Neurobiologic Processes in Drug Reward and Addiction

Adinoff

2004

Harvard Review of Psychiatry

463

274

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Neurophysiologic processes underlie the uncontrolled, compulsive behaviors defining the addicted state. These"hard-wired"changes in the brain are considered critical for the transition from casual to addictive drug use. This review of preclinical and clinical (primarily neuroimaging) studies will describe how the delineation between pleasure, reward, and addiction has evolved as our understanding of the biologic mechanisms underlying these processes has progressed. Although the mesolimbic dopaminergic efflux associated with drug reward was previously considered the biologic equivalent of pleasure, dopaminergic activation occurs in the presence of unexpected and novel stimuli (either pleasurable or aversive) and appears to determine the motivational state of wanting or expectation. The persistent release of dopamine during chronic drug use progressively recruits limbic brain regions and the prefrontal cortex, embedding drug cues into the amygdala (through glutaminergic mechanisms) and involving the amygdala, anterior cingulate, orbitofrontal cortex, and dorsolateral prefrontal cortex in the obsessive craving for drugs. The abstinent, addicted brain is subsequently primed to return to drug use when triggered by a single use of drug, contextual drug cues, craving, or stress, with each process defined by a relatively distinct brain region or neural pathway. The compulsive drive toward drug use is complemented by deficits in impulse control and decision making, which are also mediated by the orbitofrontal cortex and anterior cingulate. Within this framework, future targets for pharmacologic treatment are suggested.

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“…Cocaine is more effective than amphetamine at increasing extracellular level of serotonin release (Rothman and Baumann, 2003) and previous studies suggest that serotonin plays a key role in drug reward (see Higgins and Fletcher, 2003). For instance, blockade of serotonin type 3 receptors prevents the reward-enhancing effects of cocaine (Kelley and Hodge, 2003) but not the reward-enhancing effect of amphetamine (Montgomery et al, 1993). At the moment, however, it is not known whether the effectiveness of MPEP at reducing the reward-enhancing effect of cocaine is related to its action on serotonin neurotransmission.…”

Section: Discussionmentioning

confidence: 99%

Blockade of mGLUR5 receptors differentially alters amphetamine-induced enhancement of locomotor activity and of brain stimulation reward

Gormley

Rompré

2010

J Psychopharmacol

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This study was aimed at determining the role of mGLUR5 glutamate receptors on amphetamine-induced enhancement of locomotion and of brain stimulation reward (BSR). The effect of different doses of the mGLUR5 antagonist, MPEP (0, 1, 3 and 9 mg/kg, i.p.), was assessed on reward induced by electrical stimulation of the lateral hypothalamus, and on the enhancement of reward by amphetamine (1 mg/kg, i.p.) in adult male Long Evans rats. The effect of a single dose of MPEP (0 and 9 mg/kg) on amphetamine-induced increase in locomotor activity was also assessed. Systemic injection of MPEP alone did not alter reward threshold and maximum rate of responding. Amphetamine produced a 25-30% decrease in reward threshold, an effect not altered by the highest dose of MPEP. At this dose, MPEP produced a weak inhibition of spontaneous locomotion and a significant attenuation of the enhanced locomotor activity induced by amphetamine. These findings show that mGLUR5 glutamate receptors are unlikely to constitute important elements of the reward-relevant pathway, and do not intervene in the enhancement effect of amphetamine. They also show, however, that these glutamate receptors play a key role in amphetamine-induced increased locomotor activity, providing additional evidence for a dissociation between the substrates that mediate these two behaviours.

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The effect of a 5-HT3 receptor antagonist, ondansetron, on brain stimulation reward, and its interaction with direct and indirect stimulants of central dopaminergic transmission

Cited by 28 publications

References 31 publications

The 5 -HT3 receptor antagonists, granisetron and ondansetron, do not affect cocaine-induced shifts in intra-cranial self-stimulation thresholds

The 5 -HT3 receptor antagonists, granisetron and ondansetron, do not affect cocaine-induced shifts in intra-cranial self-stimulation thresholds

Neurobiologic Processes in Drug Reward and Addiction

Blockade of mGLUR5 receptors differentially alters amphetamine-induced enhancement of locomotor activity and of brain stimulation reward

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