The proposed research will continue ongoing studies of the neurophysiology of activity of neurons in the mesolimbic system during self-administration of cocaine. A primary question in cocaine research is the neurophysiological consequence of an elevation of dopamine in target areas of monoamine innervation. The goal of an initial series of experiments is to clarify during drug self-administration the temporal and spatial patterns of neuron population activity in subregions of the nucleus accumbens, NAC, and brain regions afferent and efferent to NAC, including medial prefrontal cortex, basolateral amygdala, ventral tegmental area and ventral pallidum. Activity in NAC and related regions will be studied using chronically implanted arrays of microwires to obtain concurrent population recordings of spike trains. Newly developed spike sorters and data analysis procedures for graphical and statistical techniques will examine concurrent activity in populations of neurons in connected areas. An initial protocol will include a simple FR5 bar press for cocaine. Protocols will also include a VR5 with light cue as a secondary reinforcer, use of delayed access to the lever, and passive doses of cocaine in similar temporal patterns as in self-administration. Activity will be studied in relation to a cocaine priming dose, and during extinction and resumption of bar press, behavior.
A second aim will be to study activity in relation to an extended task sequence, a second order VR4 lever press and VR7 for light, a task designed to extend the period of extinction and resumption of bar press behavior. Subsets of rats will be studied after training to bar press for both cocaine and heroin self-administration. Twenty-four hour recording of neuron populations will be studied in a complex environment with multiple nose poke and bar press operanda for food and water and a nose poke true reaction time task. These studies will test the hypotheses that 1) the mesolimbic system activity generates activity specific to task sequences leading to reward, 2) that sustained activity will be induced or reduced in neuron subsets in relation to extinction and resumption of behavior, 3) that activity specific to the reinforcement goal will be found in subsets of mesolimbic neurons, and 4) that prolonged neural recordings in different tasks will reveal alternate modes of coding of behavioral specificity. This research program is designed to yield a comprehensive clarification of neuron population spike train activity in the mesolimbic brain reward system during behaviors for drug self-administration reinforcement.
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