EFFECT OF NEUROLEPTIC DRUGS ON THE CONDITIONED BEHAVIOR AFTER PRETREATMENT WITH α-METHYLTYROSINE OR p-CHLOROPHENYLALANINE

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Effects of psychotropic drugs on the conditioned behavior after pretreatment with α-methyltyrosine(α-MT) or p-chlorophenylalanine(PCPA) were studied using operant conditioning technique in rodents. The operant conditioning procedure used was composed of a concurrent milk-reinforced and avoidance schedule in an operant conditioning chamber with two levers where lever pressing by rats was maintained by milk (VR 6) and electric shock (intertrial interval 1 min). Chlorpromazine (1 mg/kg i.p.), perphenazine (0.1 mg/kg i.p.), haloperidol (0.05 mg/kg i.p.) and oxypertine (0.25 mg/kg i.p.), at half of the maximum ineffective dose, respectively, caused a significant decrease in both lever pressings after pretreatment with α-MT (20 mg/kg i.p.). Such potentiating effect by α-MT was not observed with diazepam and nortriptyline. PCPA pretreatment (300 mg/kg i.p.) did not influence suppressive effects on responding under both schedules by any drug used. The one-way active avoidance procedure in mice was also employed in this study. On the avoidance response, chlorpromazine, perphenazine, haloperidol, trifluperidol, clozapine and oxypertine showed a suppressive effect, ED50 values of which were considerably lowered by pretreatment with α-MT (25 mg/kg i.p.). No influence was seen with PCPA (200 mg/kg i.p. × 2). Diazepam, phenoxybenzamine, phentolarnine, arecoline, physostigmine and clonidine also had a suppressive effect on the avoidance response, which was not influenced by pretreatment with α-MT. These results suggest that the suppressive effect of neuroleptics on the conditioned behavior is selectively potentiated by α-MT, and not influenced by PCPA.
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EFFECT OF NEUROLEPTIC DRUGS ON THE CONDITIONED BEHAVIOR AFTER PRETREATMENT WITH α-METHYLTYROSINE OR p-CHLOROPHENYLALANINE

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