Pharmacological inhibition of DA- and 5-HT activity blocks spontaneous and cocaine-activated behavior: reversal by chronic cocaine treatment.
Recently it was shown that the combined pretreatment with low autoreceptor preferring dose levels of apomorphine (0.05 mg/kg) and 8-OHDPAT (0.05 mg/kg), which decrease dopaminergic and serotonergic activity, induces a profound behavioral inhibition and also blocks the stimulant effects of cocaine. In two experiments, we report that the acute blockade of spontaneous and cocaine locomotor stimulant effects by pretreatment with 8-OHDPAT (0.05 mg/kg) plus apomorphine (0.05 mg/kg) is dose-dependently (0.0 2.5, 5.0, and 10.0 mg/kg cocaine) reversed with repeated cocaine treatments. Using a paired vs. unpaired Pavlovian conditioning protocol, we found that this reversal by cocaine (10 mg/kg) of the inhibition by the combined 8-OHDPAT plus apomorphine pretreatment occurred for the paired but not the unpaired cocaine treatment. The findings suggest that this reversal of behavioral inhibition is mediated by the transformation of the drug cues generated by 8-OHDPAT and apomorphine into cocaine-conditioned stimuli which can activate behavior.
Carey
Robert J
RJ
VA Medical Center and Upstate Medical University Syracuse, 800 Irving Avenue, Research (151), VA Medical Center, Syracuse, NY 13210, USA. Careyr@cnyrc.org
DePalma
Gail
G
Damianopoulos
Ernest
E
Shanahan
Arielle
A
Müller
Christian P
CP
Huston
Joseph P
JP
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003214:Conditioning, Classical; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D018491:Dopamine Agonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003042:Cocaine; D001058:Apomorphine; D004298:Dopamine