The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens.
Pretreatment with the serotonin-3 (5-HT3) antagonist racemic (+/-)-Zacopride hydrochloride (ZAC, 0.1 mg/kg, IP) has been previously found to completely abolish the locomotor activity induced by cocaine (10 mg/kg, IP). To determine if this effect was mediated by fluctuations in the extracellular levels of forebrain dopamine (DA), we examined the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels. Microdialysis samples were collected from the nucleus accumbens region (NAS) of awake, male, Sprague-Dawley rats. ZAC treatment alone (0.1 mg/kg, IP) did not alter DA levels relative to baseline. However, this dose of ZAC given 1 h prior to cocaine challenge (10 mg/kg, IP) caused a 27% reduction in the peak level of extracellular DA produced by cocaine, relative to saline-pretreated control animals. These results suggest that the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels may contribute to ZAC's ability to suppress cocaine-induced locomotor activity in the rat. However, additional neurochemical mechanisms are likely to be important in mediating the robust behavioral effects previously reported.
McNeish
C S
CS
Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook 11794-8790.
Svingos
A L
AL
Hitzemann
R
R
Strecker
R E
RE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology*
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012702:Serotonin Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; C055971:zacopride; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid