Blockade of the acquisition of cocaine self-administration by the NMDA antagonist MK-801 (dizocilpine).
In an attempt to assess the contribution of the NMDA receptor system to the development of cocaine self-administration, acquisition of intravenous self-administration (0.25mg/kg/infusion) was assessed in rats that received pretreatment with MK-801 (0.0, 0.1 or 0.25mg/kg). For control rats, reliable self-administration was obtained in 3-8 days of testing. These rats rapidly discriminated between depression of a lever that resulted in the delivery of cocaine and an inactive lever. Within the initial 10 day test period, most of the rats pretreated with MK-801 failed to acquire a preference for an active lever which, when depressed, resulted in a cocaine infusion: responding was generally high on both the cocaine reinforced and inactive lever. For six rats, MK-801 treatment was discontinued after 10 days. Although some of these rats had received substantial exposure to cocaine during the initial 10 days, self-administration subsequent to the termination of treatment progressed either with a time course comparable to cocaine-naive rats, or not at all. For rats that continued to receive MK-801 treatment, most failed to acquire reliable self-administration within the 18 day test period. These data suggest that the glutamatergic NMDA receptor system plays an important role in the establishment of cocaine as an effective reinforcer.
Schenk
S.
S
Texas A&M University, Department of Psychology, College Station, TX 77843, USA.
Valadez
A.
A
Worley
C.M.
CM
McNamara
C.
C