The effects of SCH 23390 and raclopride on cocaine-induced analepsis and EEG arousal in rabbits.
The effects of the dopamine D1 and D2 receptor antagonists on cocaine-induced, cholinergically-mediated analeptic and hippocampal theta activity in anesthetized rabbits were investigated. Cocaine (2 mg/kg, i.v.) reduced by 35% the duration of loss of righting reflex produced by a 25 mg/kg dose of pentobarbital. This shortening of narcosis time was blocked by pretreating the animals with the D1 antagonist, SCH 23390 (0.1 mg/kg) but not with the D2 antagonist raclopride (1-2 mg/kg). Cocaine (5 mg/kg, i.v.) also produced a short burst of increased hippocampal theta activity in urethane-anesthetized rabbits, which was also blocked by SCH 23390 but not by raclopride. An unexpected finding was that raclopride itself, at 2 mg/kg (i.v.), produced a marked activation of theta activity that lasted for 15-20 min. When cocaine was administered after this time it produced a potentiated theta response, both in duration and in magnitude. These results suggest that in the rabbit, cocaine exerts a cholinergically-mediated behavioral and EEG arousal through a D1 dopamine mechanism. The role of the D2 system is less clear but appears to be antagonistic to the D1-mediated response.
Yoshida
K
K
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
Gjerde
D K
DK
Carino
M A
MA
Halpern
L M
LM
Horita
A
A
D000704:Analysis of Variance; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D011817:Rabbits; D020891:Raclopride; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012457:Salicylamides / Q000494:pharmacology*; D013997:Time Factors
D001552:Benzazepines; D000697:Central Nervous System Stimulants; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D012457:Salicylamides; D020891:Raclopride; D003042:Cocaine