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.