Activation of 5-HT1B receptors in the nucleus accumbens reduces amphetamine-induced enhancement of responding for conditioned reward.
Previously, we have demonstrated that 5-hydroxytryptamine (5-HT) injected into the nucleus accumbens attenuates the potentiating effects of d-amphetamine on responding for conditioned reward (CR). The present studies examined the 5-HT receptor involved in this effect by investigating the effects of 5-HT agonists with differing affinities for 5-HT1 and 5-HT2 receptors on d-amphetamine-induced potentiation of responding for CR. Rats were trained to associate a light/tone stimulus (subsequently the CR) with water delivery. In a test phase, they were allowed access to a lever delivering the CR, and an inactive (NCR) lever. Responding on the CR lever was greater than responding on the NCR lever, indicating that the light/tone stimulus functioned as a CR. Responding for the CR was selectively potentiated by injections of d-amphetamine (10 microg) into the nucleus accumbens. This effect was reduced by injections into the nucleus accumbens of 5-CT (0.5 and 1 microg), RU24969 (10 microg), CP93,129 (1.25 and 2.5 microg) but not by DOI (10 microg) or 8-OH-DPAT (5 microg). The lower doses of 5-CT and CP93,129 did not reduce baseline responding for CR, or responding for water in a separate group of animals, indicating that the effects of these drugs were behaviourally selective. The higher doses abolished the CR effect, and in the case of 5-CT and RU24969 also reduced responding for water. All of the effective drugs share in common the ability to stimulate 5-HT1B receptors, albeit with differing selectivities. The effect of CP93,129, the most selective of the 5-HT1B agonists, to inhibit the response-potentiating effect of d-amphetamine was reversed by the 5-HT(1B/1D) antagonist GR127935 (3 mg/kg). The results indicate that activation of 5-HT1B receptors within the nucleus accumbens attenuates the effects of a dopamine-dependent behaviour, and that activation of these receptors can oppose the behavioural effects of elevated mesolimbic dopamine transmission.
Fletcher
P J
PJ
Department of Psychology, University of Toronto, Ontario, Canada. fletcher@psych.utoronto.ca
Korth
K M
KM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000378:metabolism*; D012201:Reward; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014867:Water / Q000494:pharmacology
D007211:Indoles; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014867:Water; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; D000661:Amphetamine