D-1 agonist, SKF 38393, but not a D-2 agonist, produces a cholinergically mediated analeptic effect in rabbits.
SKF 38393 (2-15 mg/kg, IV), but not quinpirole, shortened the duration of loss of righting reflex produced in pentobarbital-narcotized rabbits. This effect was blocked by atropine (2-5 mg/kg, IV), but not by atropine methylbromide, suggesting that a central cholinergic mechanism was involved. The analeptic effect was also blocked by SCH 23390 (0.1 mg/kg, IV) or raclopride (5 mg/kg, IV). These results indicate that SKF 38393 activates central cholinergic neurons, which in turn initiate the analeptic effect. However, the fact that raclopride also blocked the SKF 38393 analeptic effect, but quinpirole did not exert any analeptic effect, suggests that a D-1/D-2 modulation of cholinergic systems may be involved in the SKF 38393-induced analeptic effect. These results also support our earlier findings and view that cocaine-induced analeptic activity is mediated by a dopaminergic-cholinergic mechanism.
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
A
A
Horita
M A
MA
Carino
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D019257:Quinpirole; D011817:Rabbits; D020891:Raclopride; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides / Q000494:pharmacology
D001286:Atropine Derivatives; D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D019257:Quinpirole; D020891:Raclopride; D010095:Oxotremorine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001285:Atropine; C006649:methylatropine; D010830:Physostigmine; D010424:Pentobarbital