Activation of 5-HT(1B) receptors in the nucleus accumbens reduces self-administration of amphetamine on a progressive ratio schedule.
Brain serotonin interacts with dopamine function in a complex fashion. Previous work from our laboratory showed that activation of 5-HT(1B) receptors within the nucleus accumbens attenuates the ability of amphetamine to increase responding for conditioned reinforcement. The primary purpose of these experiments was to determine the impact of 5-HT receptor stimulation, with particular focus on 5-HT(1B) receptors in the nucleus accumbens on the reinforcing effect of amphetamine. To this end several experiments determined the effects of injecting 5-HT, and various 5-HT agonists, into the nucleus accumbens on responding for intravenous infusions of amphetamine (60 microg/kg) delivered according to a progressive ratio schedule of reinforcement. Both 5-HT (2.5, 5 and 10 microg) and the selective 5-HT(1B) receptor agonist CP93,129 (0.625, 1.25 and 2.5 microg) dose-dependently reduced responding for amphetamine. Injections of 5-HT but not CP93,129 also reduced responding for food under a similar PR schedule. The 5-HT(1A) agonist 8-OH-DPAT (5 microg) and the nonselective 5-HT(2) agonist DOI (10 microg) failed to alter amphetamine self-administration. Pretreatment with the selective 5-HT(1B/1D) receptor antagonist GR127935 (3 mg/kg) attenuated the ability of 5-HT and CP93,129 to reduce amphetamine self-administration following their injection into the nucleus accumbens. These results extend our previous findings that increasing 5-HT activity in the nucleus accumbens inhibits dopamine-dependent behaviour, and further indicate that activation of 5-HT(1B) receptors is particularly important in this regard.
Fletcher
Paul J
PJ
Department of Psychiatry, University of Toronto, Toronto, Canada. paul_fletcher@camh.net
Azampanah
Arezou
A
Korth
Karin M
KM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005502:Food; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects*; D012055:Reinforcement Schedule; D012646:Self Administration; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D000697:Central Nervous System Stimulants; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; C090701:GR 127935; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000661:Amphetamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine