Effects of antipsychotics ; chlorpromazine (0.25-2
mg/kg s.c.), fluphenazine (0.025-0.1
mg /k
g s.c.), haloperidol (0.013-0.05
mg/k
g s.c.) and droperidol (0.013-0.1
mg/k
g s.c.), tricyclic antidepressants ; imipramine (2.5-20
mg/k
g i.p.) and amitriptyline (5-40
mg/k
g i.p.), and anxiolitics and/or general depressants ; diazepam (0.25-2
mg/k
g s.c.), chlordiazepoxide (2.5-20
mg/k
g i.p.) and pentobarbital (2.5-20
mg/k
g s.c.) given singly and combined with d-amphetamine (1
mg/k
g s.c.) on rat's Sidmantype avoidance response (response-shock interval=30 sec, shock-shock interva 1=5 sec and 1session= 2 hr) were investigated.
All of these drugs except chlordiazepoxide suppressed the avoidance response with dose-dependent decreasing in the response (lever-pressing) rate and increasing in the shock rate. d-Ampheta mine 1
mg/k
g s.c. increased the response rate to a 2.2-2.5 times higher level than that of the saline vehicle administered control, and decreased the shock rate. The effect of d-amphetamine was dose-dependently antagonized with the antipsychotics. Here, chlorpromazine 1.3
mg/k
g, fluphenazine 0.06
mg/k
g, haloperidol 0.03
mg/k
g and droperidol 0.07
mg/k
g were estimated to inhibit perfectly the effect of d-amphetamine 1
mg/k
g. Imipramine, amitriptyline, diazepam, chlordiazepoxide and pentobarbital enhanced the response-increasing effect of d-amphetamine, in all doses except pentobarbital by more than 10
mg/k
g. The doses which elicited the maximum increase in the response rate were imipramine 10
mg/k
g, amitriptyline 10
mg/k
g, diazepam 0.5
mg/k
g, chlordiazepoxide 10
mg/k
g and pentobarbital 5
mg/k
g.
The present experiment demonstrated that d-amphetamine antagonized specifically with antipsychotics while not with antidepressants, anxiolitics and/or general depressants. These results suggest that the Sidman-type avoidance test in which drugs are given in combination with amphetamine is applicable to assess the pharmacological properties of psychotropic drugs in detail.
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