5-HT1A agonists and dopamine: the effects of 8-OH-DPAT and buspirone on brain-stimulation reward

J Neural Transm Gen Sect. 1991;83(1-2):139-48. doi: 10.1007/BF01244460.

Abstract

Two specific 5-HT1A agonists, 8-OH-DPAT (0-300 micrograms/kg), and buspirone (0-3.0 mg/kg), were tested on variable-interval, threshold-current self-stimulation of rat lateral hypothalamus. Buspirone produced a prolonged monotonic depression of responding, whereas the effects of 8-OH-DPAT were biphasic: 3.0 micrograms/kg produced a sustained enhancement of responding while higher doses (100-300 micrograms/kg) produced a relatively short-lasting depression. This biphasic pattern parallels previously reported effects of 8-OH-DPAT on food intake and on various other behaviours. Threshold-current self-stimulation is highly sensitive to alterations in dopaminergic transmission but relatively insensitive to changes in 5-HT. Thus the facilitatory effect of low-dose 8-OH-DPAT seems most plausibly interpreted in terms of enhanced dopaminergic transmission. This could be brought about by 5HT1A autoreceptor-mediated inhibiton of 5-HT release and consequent disinhibition of dopaminergic transmission. Depression of self-stimulation by higher doses of 8-OH-DPAT may reflect the activity of 8-OH-DPAT at postsynaptic 5-HT receptors, with consequent inhibition of DA transmission. Suppression of responding after buspirone at all doses tested may reflect the action of this compound as a partial agonist at postsynaptic 5-HT receptors, and/or its effects on other systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Animals
  • Arousal / drug effects
  • Buspirone / administration & dosage
  • Buspirone / pharmacology*
  • Dopamine / physiology*
  • Dose-Response Relationship, Drug
  • Feeding Behavior / drug effects
  • Hypothalamus / drug effects*
  • Hypothalamus / physiology
  • Male
  • Rats
  • Receptors, Dopamine / drug effects
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology
  • Reward*
  • Self Stimulation / drug effects*
  • Self Stimulation / physiology
  • Serotonin / physiology*
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • Receptors, Dopamine
  • Receptors, Serotonin
  • Tetrahydronaphthalenes
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Buspirone
  • Dopamine