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MK‐801 (Dizocilpine): Synergist and conditioned stimulus in bromocriptine‐induced psychomotor sensitization
Author(s) -
Wise Roy A.,
Mendrek Adrianna,
Carlezon William A.
Publication year - 1996
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199604)22:4<362::aid-syn7>3.0.co;2-9
Subject(s) - sensitization , bromocriptine , dizocilpine , nmda receptor , agonist , catalepsy , pharmacology , amphetamine , dopamine agonist , conditioned place preference , apomorphine , behavioral sensitization , dopamine , chemistry , anesthesia , medicine , endocrinology , morphine , receptor , hormone , nucleus accumbens , immunology , haloperidol , prolactin
Intraperitoneal injections of the D 2 /D 3 dopamine agonist bromocriptine (5.0 mg/kg, IP) induced locomotion that became progressively stronger on successive days of testing. The sensitized response developed twice as rapidly when the non‐competitive NMDA antagonist MK‐801 (0.25 mg/kg, IP) was given 30 min after bromocriptine (so that the peak effects of the two drugs overlapped). In a second group of animals, MK‐801 was given 30 min prior to bromocriptine (the pretreatment regimen typical of studies where MK‐801 is reported to block cocaine, amphetamine or morphine sensitization) and locomotion was monitored during the pretreatment period; in this case sensitization to the locomotor‐stimulating effects of MK‐801 alone (in the pretreatment period) as well as sensitization to the locomotor‐stimulating effects of the drug combination (following the second injection) were observed. No sensitization to the effects of MK‐801 alone (pretreatment) were seen in animals that received saline rather than bromocriptine as their second injection in this experiment. Thus MK‐801 does not block but rather enhances bromocriptine sensitization; it appears to do so by a synergism with the locomotor effects of bromocriptine and by becoming a conditioned stimulus for the sensitized response. These findings confirm the earlier report that NMDA receptor activation is not critical to bromocriptine‐induced sensitization, and they illustrate the importance of controls for conditioning and state‐dependency phenomena in studies of drug interactions in psychomotor sensitization. © 1996 Wiley‐Liss, Inc.