MK-801 DISRUPTS THE EXPRESSION BUT NOT THE DEVELOPMENT OF BROMOCRIPTINE SENSITIZATION - A STATE-DEPENDENCY INTERPRETATION

Repeated administration of the D-2-type agonist bromocriptine (5.0 mg/ kg, IP) caused progressive increases in the locomotor-stimulating effe cts of the drug in rats. Similar progressive increases in locomotor ac tivity were observed in rats that received repeated coadministration o f the NMDA receptor antagonist MK-801 (0.25 mg/kg, IP) plus bromocript ine. However, when rats previously treated with the combination of dru gs received either bromocriptine or MK-801 alone, their levels of acti vity were comparable to those of rats having no prior experience with either drug. A second group of rats was sensitized to the effects of b romocriptine alone; no evidence of bromocriptine sensitization was see n when MK-801 was subsequently coadministered with bromocriptine. Thus , either the presence or the absence of MK-801 could-depending upon th e conditions of previous drug treatment-block the expression of bromoc riptine sensitization. When a third group of rats was sensitized to th e combination of MK-801 plus bromocriptine and subsequently tested fol lowing 2 or 6 drug-free weeks, evidence of sensitized responses was st ill present. Thus, at the very least, blockade of NMDA receptors with MK-801 fails to compromise the cellular changes associated with sensit ization to the repeated combination of MK-801 plus bromocriptine. Brom ocriptine sensitization may prove to be unique in this regard, but the present findings suggest a control condition that should be carefully explored in studies of the effects of MK-801 on sensitization involvi ng other stimulant drugs. (C) 1995 Wiley-Liss, Inc.