Effect of repeated haloperidol administration on phencyclidine discrimination in rats.
1. Previous research has shown that acute doses of haloperidol block many of themotor stimulatory effects of phencyclidine (PCP) and other PCP-like drugs. In addition, when given acutely, haloperidol produces partial attenuation of PCP's discriminative stimulus effects in rats. 2. Haloperidol is often administered chronically in clinical situations; hence, it is important to investigate the effects of repeated, as well as acute, dosing with this drug. 3. The purpose of the present study was to examine the effects of repeated administration of haloperidol on PCP discrimination in rats. Rats were trained to discriminate PCP (2.0 mg/kg) from saline in a two-lever drug discrimination procedure and were tested with cumulative doses of PCP before and after repeated administration of saline and of haloperidol (0.5 mg/kg/day). 4. Discrimination training was suspended during the two 14-15-day repeated dosing regimens. Suspended training with repeated saline administration had little effect on the dose-effect curve for % PCP-lever responding. 5. Repeated administration of haloperidol produced some diminution of PCP discrimination. After haloperidol, the ED50 for % PCP-lever responding was 1.4 mg/kg, compared to the pre-haloperidol ED50 of 0.7 mg/kg. 6. These results are consistent with those of acute dosing studies with haloperidol in PCP-trained rats and suggest that repeated administration of haloperidol may disrupt PCP's discriminative stimulus effects, although most rats were still able to discriminate the higher doses of PCP.
Wiley
J L
JL
Department of Pharmacology & Toxicology Virginia Commonwealth University Medical College of Virginia Richmond, USA.
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D010622:Phencyclidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D010622:Phencyclidine; D006220:Haloperidol