TY - JOUR
T1 - Evidence of a central mechanism mediating tolerance to the discriminative stimulus properties of cocaine
AU - Wood, Douglas M.
AU - Retz, Konrad C.
AU - Emmett-Oglesby, Michael W.
PY - 1987/11
Y1 - 1987/11
N2 - Rats were trained to detect intraperitoneal (IP) administration of cocaine, 10.0 mg/kg, using a two-lever choice discrimination procedure. Following training, cocaine was generalized to the cocaine training stimulus in a dose-dependent manner. Subsequently, bilateral cannulae were implanted in the lateral ventricles in ten animals, and intracerebroventricular (ICV) administration of cocaine was also generalized to the IP training dose in a dose-dependent manner with maximum generalization occurring with 80 μg cocaine. After baseline testing, training was halted and cocaine, 20 mg/kg/8-hr, was injected chronically in all rats for 6 days, and then the dose-effect curve for generalization of cocaine was redetermined. Chronic administration of cocaine significantly shifted the dose-effect curve three-fold to the right for both IP and ICV routes of administration. These data suggest that the stimulus properties of cocaine administered centrally are generalized in rats trained by peripheral administration and supports the hypothesis of central mediation of the cocaine stimulus. Also, the comparable shift of the cocaine dose-effect curve following chronic cocaine administration suggests that a central pharmacodynamic mechanism mediates tolerance to the discriminative stimulus properties of cocaine.
AB - Rats were trained to detect intraperitoneal (IP) administration of cocaine, 10.0 mg/kg, using a two-lever choice discrimination procedure. Following training, cocaine was generalized to the cocaine training stimulus in a dose-dependent manner. Subsequently, bilateral cannulae were implanted in the lateral ventricles in ten animals, and intracerebroventricular (ICV) administration of cocaine was also generalized to the IP training dose in a dose-dependent manner with maximum generalization occurring with 80 μg cocaine. After baseline testing, training was halted and cocaine, 20 mg/kg/8-hr, was injected chronically in all rats for 6 days, and then the dose-effect curve for generalization of cocaine was redetermined. Chronic administration of cocaine significantly shifted the dose-effect curve three-fold to the right for both IP and ICV routes of administration. These data suggest that the stimulus properties of cocaine administered centrally are generalized in rats trained by peripheral administration and supports the hypothesis of central mediation of the cocaine stimulus. Also, the comparable shift of the cocaine dose-effect curve following chronic cocaine administration suggests that a central pharmacodynamic mechanism mediates tolerance to the discriminative stimulus properties of cocaine.
KW - Cocaine
KW - Discriminative stimulus
KW - Rats
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=0023513223&partnerID=8YFLogxK
U2 - 10.1016/0091-3057(87)90461-8
DO - 10.1016/0091-3057(87)90461-8
M3 - Article
C2 - 3685076
AN - SCOPUS:0023513223
SN - 0091-3057
VL - 28
SP - 401
EP - 406
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
IS - 3
ER -