MK-801 disrupts the expression but not the development of bromocriptine sensitization: a state-dependency interpretation.
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.
Carlezon
W A
WA
Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.
Mendrek
A
A
Wise
R A
RA
D000818:Animals; D001971:Bromocriptine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D016194:Receptors, N-Methyl-D-Aspartate; D001971:Bromocriptine; D016291:Dizocilpine Maleate