Cocaine treatment increases extracellular cholecystokinin (CCK) in the nucleus accumbens shell of awake, freely moving rats, an effect that is enhanced in rats that are behaviorally sensitized to cocaine.
Cholecystokinin (CCK) is co-localized with dopamine, is known to modulate dopamine neurotransmission and is involved in behavioral sensitization to psychostimulants. To better understand its role, CCK was measured by microdialysis in the nucleus accumbens (NAC) shell in response to cocaine in drug-naive rats and in rats that are behaviorally sensitized to cocaine. Basal extracellular levels of CCK in drug-naive rats were 0.17 pg/20 min fraction, while in cocaine-sensitized rats, they were significantly higher (0.56 pg). Treating drug-naive rats with cocaine caused a significant increase in CCK to 0.58 pg. Cocaine treatment of cocaine-sensitized rats increased CCK to 0.98. When analyzed as a function of time after cocaine treatment, these increases were sustained and were significantly different from CCK levels of saline-treated rats. In cocaine-sensitized rats, CCK levels following cocaine treatment were also significantly higher than levels in drug-naive animals receiving a single injection of cocaine. These results provide evidence for an activation of the mesolimbic and/or cerebral cortical CCK system in response to repeated cocaine administration. These results provide a neurochemical basis for an important role of CCK (via modulation of dopamine neurotransmission) in expression of cocaine sensitization.
Beinfeld
Margery C
MC
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. Margery.Beinfeld@tufts.edu
Connolly
Kelly J
KJ
Pierce
R Christopher
RC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002766:Cholecystokinin / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014851:Wakefulness
D002766:Cholecystokinin; D003042:Cocaine