MK‐801 Disrupts the expression but not the development of bromocriptine sensitization: A state‐dependency interpretation

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Abstract
Repeated administration of the D2‐type agonist bromocriptine (5.0 mg/ kg, IP) caused progressive increases in the locomotor‐stimulating effects of the drug in rats. Similar progressive increases in locomotor activity were observed in rats that received repeated coadministration of the NMDA receptor antagonist MK‐801 (0.25 mg/ kg, IP) plus bromocriptine. However, when rats previously treated with the combination of drugs received either bromocriptine or MK‐801 alone, their levels of activity were comparable to those of rats having no prior experience with either drug. A second group of rats was sensitized to the effects of bromocriptine alone; no evidence of bromocriptine sensitization was seen when MK‐801 was subsequently coadministered with bromocriptine. Thus, either the presence or the absence of MK‐801 could—depending upon the conditions of previous drug treatment—block the expression of bromocriptine sensitization. When a third group of rats was sensitized to the combination of MK‐801 plus bromocriptine and subsequently tested following 2 or 6 drug‐free weeks, evidence of sensitized responses was still present. Thus, at the very least, blockade of NMDA receptors with MK‐801 fails to compromise the cellular changes associated with sensitization to the repeated combination of MK‐801 plus bromocriptine. Bromocriptine 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 involving other stimulant drugs.