Brain neurotransmitter turnover rates during rat intravenous cocaine self-administration.
The turnover rates of dopamine, norepinephrine, serotonin, aspartate, glutamate and GABA were measured in 27 brain regions of rats self-administering cocaine and in yoked cocaine- and yoked vehicle-infused controls using radioactive pulse-labeling procedures to identify brain neuronal systems underlying self-administration. Changes in the activity of heretofore unrecognized dopamine, norepinephrine, serotonin, glutamate and GABA innervations of the forebrain specific to cocaine self-administration were found. This included innervations of the nucleus accumbens, ventral pallidum, lateral hypothalamus and the anterior and posterior cingulate, entorhinal-subicular and visual cortices. Turnover rates also were calculated using metabolite/neurotransmitter ratios which were inconsistent with the pulse-label technologies indicating that ratio procedures are not accurate measures of neurotransmitter utilization. Results with the pulse-label technique provide evidence of the involvement of neuronal systems in cocaine self-administration not previously known, some of which may have a broader role in brain reinforcement processes for natural reinforcers (i.e. food, water, etc.) since drugs of abuse are thought to produce reinforcing effects by modulating activity in these endogenous systems.
Smith
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Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA. jasmith@wfubmc.edu
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D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012646:Self Administration / Q000523:psychology
D018377:Neurotransmitter Agents; D003042:Cocaine; D004298:Dopamine