Serotonin 5-HT(2C) receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine.
The serotonin 5-HT(2C) receptor (5-HT(2C)R) is abundant in the nucleus accumbens (NAc) shell and is considered an important target for 5-HT to modulate the dopamine (DA) mesoaccumbens circuit, which plays a prominent role in the behavioral effects of cocaine. The present study analyzed the ability of intra-NAc shell infusions of the 5-HT(2C)R agonists, MK 212 and RO 60-0175, or the 5-HT(2C)R antagonist, RS 102221, to alter either spontaneous or cocaine-evoked activity as well as the discriminative stimulus properties of cocaine. In male Sprague--Dawley rats implanted with bilateral cannulae aimed at the NAc shell, locally injected MK 212 (0.05--0.5 microg/side) or RO 60-0175 (0.5--5 microg/side) did not alter spontaneous activity, but dose-dependently enhanced hyperactivity evoked by cocaine (10 mg/kg ip). In rats trained to discriminate cocaine (10 mg/kg ip) from saline (ip) in a two-lever, water-reinforced FR 20 task, intra-NAc microinfusion of MK 212 (0.05 microg/side) or RO 60-0175 (0.5 microg/side) evoked 37% or 48% cocaine lever responding, respectively. Both MK 212 (0.05 microg/side) and RO 60-0175 (0.5 microg/side) enhanced the discriminability of submaximal doses of cocaine (0.625--2.5 mg/kg). Moreover, intra-NAc infusion of RS 102221 (0.05--1.5 microg/side) dose-dependently attenuated the stimulus effects of cocaine. These data reinforce the hypothesis that 5-HT(2C)R plays a role in the regulatory neurochemistry of the NAc shell that is important to the full expression of the behaviors evoked by cocaine.
Filip
Malgorzata
M
Institute of Pharmacology, Polish Academy of Sciences, 31-343, Cracow, Poland.
Cunningham
Kathryn A
KA
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced* / Q000523:psychology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000502:physiology*; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D018765:Dopamine Uptake Inhibitors; D005021:Ethylamines; D007211:Indoles; D011719:Pyrazines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; C103848:Ro 60-0175; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D013449:Sulfonamides; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D003042:Cocaine