RU-24969 disrupts d-amphetamine self-administration and responding for conditioned reward via stimulation of 5-HT1B receptors

Behav Pharmacol. 1999 Mar;10(2):183-93. doi: 10.1097/00008877-199903000-00007.


Behavioural and neurochemical evidence indicates a facilitatory effect of 5-hydroxytryptamine (5-HT), acting via 5-HT1B receptors, on dopamine (DA) systems. To explore this interaction further, these experiments examined the effects of the 5-HT1A/1B agonist RU-24969 on behaviours known to involve the mesolimbic DA system. These behaviours were locomotor activity, intravenous self-administration of d-amphetamine, responding for a conditioned reward (CR), and the response potentiating effects of amphetamine on CR responding. Locomotor activity was enhanced by 1 and 3 mg/kg RU 24969, and both doses also reduced responding for d-amphetamine (60 microg/kg/infusion). Changing the unit dose produced a characteristic U-shaped dose-response curve. This dose-response relationship was not apparent following injection of RU-24969. Across all unit infusion doses of amphetamine, the level of responding was fairly constant. In the CR experiments, rats responded for a conditioned stimulus that was previously paired with water. RU-24969 completely disrupted responding for CR, and also abolished CR responding in rats injected with 3 microg d-amphetamine in the nucleus accumbens. RU-24969 also markedly suppressed responding for water. The suppressant actions of RU-24969 on amphetamine self-administration and CR responding involve stimulation of 5-HT1B receptors, since they were reversed by the 5-HT1B/1D antagonist GR 127935 (3 mg/kg), but not by the 5-HT1A antagonist WAY-100635 (1 mg/kg). None of the behavioural effects of RU-24969 are consistent with a selective action to enhance mesolimbic DA function. Rather, global activation of 5-HT1B receptors appear to exert a general disruptive effect on operant responding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine-Related Disorders / prevention & control*
  • Animals
  • Central Nervous System Stimulants* / administration & dosage
  • Conditioning, Operant / drug effects*
  • Dextroamphetamine* / administration & dosage
  • Dose-Response Relationship, Drug
  • Indoles / pharmacology*
  • Male
  • Microinjections
  • Motor Activity / drug effects
  • Nucleus Accumbens
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin / drug effects*
  • Reward
  • Self Administration
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology*
  • Water


  • Central Nervous System Stimulants
  • Indoles
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Water
  • 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • Dextroamphetamine