Involvement of 5-HT(3) receptors in the nucleus accumbens in the potentiation of cocaine-induced behaviours in the rat.
1. The present study investigated the central effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the role of 5-hydroxytryptamine(3) (5-HT(3)) receptors in the core of the nucleus accumbens (NAc) on cocaine-induced behavioural changes in rats. 2. The 5-HT(3) receptor antagonist ondansetron (1 or 10 ng) was microinjected bilaterally into the core of the NAc 60 min prior to peripheral cocaine (15 mg kg(-1), i.p.) administration followed by the assessment of locomotor activity, rearing activity and head bobs. Both doses of ondansetron attenuated cocaine's stimulatory effect on behaviours. 3. Fluoxetine (0.05 or 5 microg) microinjected bilaterally into the core of the NAc 30 min before peripheral administration of cocaine produced dose-dependent biphasic effects on cocaine-induced behaviours. Intra-NAc administration of 0.05 microg fluoxetine resulted in a potentiation of cocaine-induced behaviours, while the higher dose of the SSRI (5 microg) attenuated the stimulant effect of cocaine on behaviours. 4. To investigate a possible involvement of 5-HT(3) receptors in fluoxetine's facilitatory action, ondansetron (10 ng) was microinjected 30 min prior to fluoxetine (0.05 microg), which resulted in a significant attenuation of the facilitatory effect of fluoxetine on cocaine-induced behaviours. 5. Thus, 5-HT(3) receptors in the core of the NAc appear to mediate stimulatory effects on cocaine-induced locomotor activity, rears and head bobs, whereas the attenuation of cocaine-induced behaviours by fluoxetine at the higher dose, suggests the involvement of a different 5-HT receptor subtype.
Herges
S
S
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
Taylor
D A
DA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors
D003042:Cocaine; D005473:Fluoxetine; D017294:Ondansetron; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors