[Effects of muscimol on aggressive behaviors induced by clonidine in mice].
A behavioral study was carried out to clarify a relationship between the GABAergic and purinergic central system in aggressive behaviors induced by clonidine in mice. Mice administered a high dose of clonidine (20 mg/kg, i.p.) exhibited aggressive behaviors such as biting and attacking. These behaviors are inhibited by L-PIA (N6-L-phenylisopropyl adenosine) and stimulated by caffeine, which suggest that a blockade of adenosine receptors is involved in these behaviors. Muscimol (0.5-2 mg/kg, i.p.), a GABA-a receptor agonist, not only markedly potentiated clonidine (20 mg/kg i.p.)-induced aggressive behaviors but also elicited characteristic behaviors such as gnawing, reinforced irritability, and self-mutilation. Bicuculline (1, 2 mg/kg, i.p.), a GABA-a receptor antagonist, or picrotoxin (1 mg/kg, i.p.), a chloride channel blocker, did not significantly affect clonidine (20 mg/kg, i.p.)-induced aggressive behaviors. The potentiating effects of muscimol (0.5, 1 mg/kg, i.p.) on clonidine-induced aggressive behaviors were antagonized by bicuculline (1, 2 mg/kg, i.p.), but not affected significantly by picrotoxin (1 mg/kg, i.p.). L-PIA (0.2 mg/kg, i.p.) reduced clonidine-induced aggressive behaviors and also reversed the potentiating effects of muscimol. Stereotyped gnawing behaviors induced by combined treatment of muscimol (0.5, 1 mg/kg, i.p.) and clonidine (20 mg/kg, i.p.) were not affected by bicuculline (2 mg/kg, i.p.). The results suggest that the potentiating effects of muscimol on clonidine-induced aggressive behaviors may be induced via the stimulation of GABA-a receptors, although not necessarily associated with chloride channel functions, and may involve certain interactions between the stimulation of GABA-a receptors and the inhibition of adenosine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaneyuki
H
H
Department of Neuropsychiatry, Yamaguchi University School of Medicine, Ube, Japan.
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001640:Bicuculline / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009118:Muscimol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology*
D001640:Bicuculline; D003000:Clonidine; D009118:Muscimol; D010852:Picrotoxin; D011963:Receptors, GABA-A