Behavioral effects of dilazep on cholinergic, dopaminergic, and purinergic systems in the rat.
This study examined the effects of 1,4-bis[3-(3,4,5-trimethoxy benzoyloxy)-propyl] perhydro-1,4-diazepine (dilazep; Comelian) on central dopaminergic, cholinergic, and purinergic neuronal systems in rats. Intraperitoneal injections of dilazep (1-5 mg/kg) produced yawning responses, the most effective dose being 2 mg/kg. Dilazep potentiated physostigmine-induced yawning but not pilocarpine- and bromocriptine-induced yawning. Dilazep-induced yawning was not affected by low doses of haloperidol or sulpiride, but was completely inhibited by atropine, a muscarinic M1 receptor antagonist. Dilazep-induced yawning, as well as physostigmine-induced yawning, were markedly inhibited by pretreatment with SK & F 38393, a dopamine D1 receptor agonist, and were potentiated by SCH23390, a dopamine D1 receptor antagonist that alone does not elicit yawning. Caffeine, an adenosine receptor antagonist, inhibited dilazep- and physostigmine-induced yawning responses but N6-cyclohexyl adenosine (CHA) and N6-(L-phenylisopropyl, adenosine (L-PIA), adenosine A1 receptor agonists, were inactive. These results suggest that because the effects of dilazep on central cholinergic neurons are similar to those of physostigmine dilazep may potentiate indirectly the action of endogenous acetylcholine. Cholinergic neurons activated by dilazep may be modulated by postsynaptic dopamine D1 receptor activity but may not be affected by dopamine D2 receptor activity. Furthermore, the stimulatory effects of dilazep on cholinergic neuron may not be due to an inhibition of dopamine D1 receptors via purinergic (adenosine A1 receptor) stimulation by dilazep.
Department of Neuropsychiatry, Yamaguchi University School of Medicine, Ube, Japan.
I
I
Ushijima
Y
Y
Mizuki
T
T
Ukita
H
H
Kaneyuki
S
S
Inano
M
M
Yamada
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001971:Bromocriptine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004109:Dilazep / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010277:Parasympathomimetics / Q000494:pharmacology; D010830:Physostigmine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010862:Pilocarpine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015000:Yawning / Q000187:drug effects
D015259:Dopamine Agents; D010277:Parasympathomimetics; D011687:Purines; D010862:Pilocarpine; D001971:Bromocriptine; D010830:Physostigmine; D004109:Dilazep; D004298:Dopamine