The 5-HT1A receptor modulates the effects of cocaine on extracellular serotonin and dopamine levels in the nucleus accumbens.
The regulation of extracellular levels of serotonin (5-HT) and dopamine in response to cocaine by 5-HT1A receptors was examined using in vivo microdialysis and the 5-HT1A receptor antagonist 4-(2'-methoxy-)-phenyl-1-[2'-(N-2''-pyridinyl)-p-fluorobenzamido-]ethyl-piperazine (p-MPPF). Pretreatment with p-MPPF significantly augmented the increase in extracellular levels of both 5-HT and dopamine in the nucleus accumbens produced by systemic administration of cocaine. Levels of 5-HT or dopamine were unaffected by p-MPPF given alone. Extracellular levels of 5-HT and dopamine were increased dramatically by cocaine infused locally into the nucleus accumbens. Systemic injection of cocaine given during the cocaine infusion reduced 5-HT and dopamine levels, presumably by activating inhibitory 5-HT and dopamine autoreceptors outside of the locus of infusion. The reduction of 5-HT and dopamine levels by systemic cocaine during accumbal infusion was blocked by pretreatment with the 5-HT1A receptor antagonist p-MPPF. Taken together, these findings suggest that the 5-HT1A autoreceptor acts to modulate the effects of cocaine on both 5-HT and dopamine levels in the nucleus accumbens.
Andrews
Christine M
CM
Institute of Neurological Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kung
Hank F
HF
Lucki
Irwin
I
D000631:Aminopyridines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D013997:Time Factors
D000631:Aminopyridines; D010879:Piperazines; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C099463:4-(2' methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-fluorobenzamido)ethyl)piperazine; D003042:Cocaine; D004298:Dopamine