5-HT1A agonists and dopamine: the effects of 8-OH-DPAT and buspirone on brain-stimulation reward.
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.
Montgomery
A M
AM
Institute of Neurology, National Hospital, London, United Kingdom.
Rose
I C
IC
Herberg
L J
LJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001143:Arousal / Q000187:drug effects; D002065:Buspirone / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone; D004298:Dopamine