Abstract

Phencyclidine (PCP) sensitivity of rats, whose body weights were maintained at 70% of free-feeding controls, was compared to drug sensitivity on the controls in terms of unconditioned (exploratory) behavior and plasma corticosterone levels. Low doses of PCP HCl [0 (saline vehicle), 0.3 or 0.9 mg/kg, SC] were given to food-deprived rats and to free-feeding controls 15 minutes before measuring unconditioned behavior for 90 minutes; then PCP in brain and corticosterone in plasma were assayed. An additional group (0.43 mg/kg) was established from the reduced-weight rats in order to compare with free-feeding rats given 0.3 mg/kg, the same absolute dose—a circumstance reflecting “street” usage in which doses are not adjusted for body weight differences among users. These low doses of PCP altered exploratory behaviors, but there did not appear to be an interaction between food-deprivational status and drug, with the possible exception of an altered effect of PCP upon habituation in the lighter animals. PCP elevated plasma corticosterone levels over saline controls only in the reduced-weight rats. The drug, possibly reflecting a tranquilizing action of the lowest dose, reduced corticosterone levels in free-feeding controls. Brain levels of drug were directly related to dose, and were elevated in the food-deprived animals 26–30% over those at the same per-weight dose levels in the free-feeding rats, in spite of being given lower absolute amounts of drug. In the 0.43 mg/kg reduced-weight dose group, given the same absolute dose as the 0.3 mg/kg free-feeding group, brain levels were doubled over the latter group, and exploratory behavior was correspondingly different from the free-feeding group. Behavioral and endocrinological consequences of lipophilic drugs (like PCP) are magnified in states of weight loss with fixed-amount dose regimens, and this might have a dispositional basis.

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