KAPPA-OPIOID-MEDIATED BEHAVIORAL SENSITIZATION IN THE PREWEANLING RAT- RELATIONSHIP TO FOS IMMUNOREACTIVITY

When given acutely, drugs that stimulate kappa opioid receptors (e.g., U-50,488) enhance the locomotor activity of preweanling rats and indu ce regional increases in Fos immunoreactivity (IR). In contrast, the e ffects of chronic treatment with kappa opioid agonists are unknown. Th e purpose of the present study was two-fold: first, to determine wheth er repeated treatment with a kappa opioid agonist would sensitize the locomotor activity of preweanling rats and, second, to determine wheth er changes in Fos LR correspond with the occurrence of locomotor sensi tization. To test these hypotheses, rats were injected with U-50,488 ( 5 mg/kg, SC) or saline on either postnatal days (PD) 5-9 or PD 11-15. For rats pretreated on PD 5-9, a test day injection of U-50,488 or sal ine was given after either 1 or 7 abstinence days (i.e., at PD 11 or P D 17). For rats pretreated on PD 11-15, a test day injection of U-50,4 88 or saline was given after I abstinence day (i.e., at PD 17). In two additional experiments, the acute and chronic effects of U-50,488 tre atment were assessed in adult rats. As expected, repeated treatment wi th U-50.488 produced locomotor sensitization at both PD Il and PD 17, but only when the test day occurred I, and not 7, days after cessation of drug pretreatment. Thus, the persistence of the sensitized respons e was very brief. Test clay treatment with U-50,488 stimulated Fos IR in various brain regions of the preweanling rat, including the me dial striatum, nucleus accumbens, lateral habenula, and septal area. Chron ic treatment with U-50,488 depressed Fos expression in a number of bra in regions (relative to acutely treated rats); however these changes i n Fos IR did not necessarily coincide with the occurrence of behaviora l sensitization. Repeated treatment with U-50,488 did not produce loco motor sensitization in adult rats, so Fos IR was not assessed in this age group. Therefore, while acute treatment with U-50,488 both increas ed locomotor activity and stimulated Fos IR in preweanling rats, chron ic U-50,488 treatment produced be behavioral changes that did not corr espond with Fos expression.