Relationship of cocaine-induced c-Fos expression to behaviors and the role of serotonin 5-HT2A receptors in cocaine-induced c-Fos expression.
Serotonin 5-HT2A receptor antagonists have been shown to attenuate the locomotor stimulant effects of cocaine in rats. The present study used the expression of c-Fos protein as a marker to identify brain areas through which 5-HT2A receptors may modulate cocaine-induced behaviors. Significant correlations were observed between cocaine-induced hyperactivity and c-Fos expression in the nucleus accumbens core (NAcC), caudate-putamen (CPu), and subthalamic nucleus. In a separate experiment, a low, behaviorally relevant dose of cocaine was found to increase c-Fos immunoreactivity in the medial CPu, NAcC, and nucleus accumbens shell (NAcSh). The selective 5-HT2A receptor antagonist M100907 significantly attenuated cocaine-induced c-Fos expression in the medial CPu and in the NAcSh. These data suggest that 5-HT2A receptors in the NAcSh and CPu or in afferents to these regions may contribute to genomic responses to cocaine in the brain as well as to cocaine-induced locomotor activity.
Szucs
Regina P
RP
Department of Pharmacology and Toxicology Center for Addiction Research, University of Texas Medical Branch., Galveston, TX, USA.
Frankel
Paul S
PS
McMahon
Lance R
LR
Cunningham
Kathryn A
KA
D000704:Analysis of Variance; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D002452:Cell Count / Q000379:methods; D003042:Cocaine / Q000008:administration & dosage*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005464:Fluorobenzenes / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D018765:Dopamine Uptake Inhibitors; D005464:Fluorobenzenes; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; C079049:volinanserin; D003042:Cocaine