Intracranial cocaine self-administration into the medial prefrontal cortex increases dopamine turnover in the nucleus accumbens.
Adult male rats were trained to intracranially self-administer cocaine (50-100 pmol/100 nl infusion) into the medial prefrontal cortex and to simultaneously deliver an infusion of vehicle (100 nl of artificial cerebrospinal fluid) to a littermate control. When stable base lines of responding were obtained, each rat was implanted with an indwelling jugular catheter for the administration of radioactive precursors for the biogenic amine neurotransmitters. When stable rates of responding were re-established, the animals were infused with the radiolabeled precursors at the beginning of the behavioral session and were sacrificed 60 or 90 min later. Discrete response-contingent infusions of cocaine into the medial prefrontal cortex resulted in decreases in the turnover of dopamine and serotonin and increases in norepinephrine utilization at the site of self-injection compared to vehicle-infused controls. In contrast, DA turnover was significantly increased in the ipsilateral nucleus accumbens of the self-administering rats. These data demonstrate that discrete response-contingent cocaine infusions into the medial prefrontal cortex activate DA innervations of the nucleus accumbens, likely through descending pathways affecting A10 dopaminergic cell bodies, suggesting that neuronal activity similar to that observed after i.v. self-administration is initiated with the ICSA of the drug.
Department of Pharmacology & Therapeutics, Louisiana State University Medical Center, Shreveport.
N E
NE
Goeders
J E
JE
Smith
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex; D051381:Rats; D011916:Rats, Inbred F344; D012646:Self Administration; D014443:Tyrosine / Q000378:metabolism
D015102:3,4-Dihydroxyphenylacetic Acid; D014443:Tyrosine; D003042:Cocaine; D004298:Dopamine