Role of the ventral tegmental area, cannabinoid receptors and GABA neurons in motor activity

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Title: Role of the ventral tegmental area, cannabinoid receptors and GABA neurons in motor activity
Author: Erik Justin Shank
Abstract: Illicit abuse of psychoactive substances , including marijuana , continues to be a serious problem in our society and therefore cultivating a more thorough understanding of the neuroanatomical and neurochemical substrates underlying drug abuse is needed . Characterizing specific brain nuclei that are integral components of brain reward circuits , such as the ventral tegmental area (VTA ) , may offer important insights into modulation of behaviors associated with drug abuse . The VTA includes DA -containing and GABA -containing neurons which provide important forebrain control over the limbic system . The present series of studies explored these VTA neurons from two perspectives : First , we explored the VTA as a potential site of action for cannabinoid receptors (CB1R ) and provide the first detailed analysis of the distribution of CB1R throughout the various subnuclei and across the rostrocaudal extent of the VTA . We demonstrated that CB1R populations have postsynaptic localization in the VTA , and a rostrocaudal gradient of expression in the interfascicular nucleus , which expressed the highest level of CB1R in the VTA subnuclei . Second , we explored the prospect that specific ablation of a subset of VTA neurons , those GABA -containing neurons that posses & #61549 ; -opioid receptors , play an important role in the generation of motor behavior . Ablation of GABA neurons following intra -VTA administration of the selective toxin dermorphin -saporin was associated with elevated spontaneous locomotor activity at day 7 that normalized to basal levels by day 14 after treatment . Despite this normalization motor hyperactivity induced by the well -characterized psychostimulant cocaine was significantly elevated in keeping with the hypothesis that loss of GABAergic innervation in the VTA sensitizes to the neurochemical actions of cocaine . Collectively , our results demonstrate a new localization of CB1R in the VTA and the behavioral impact of GABA -containing neuron ablation in the VTA . These data add to growing evidence of the impact of psychoactive substances on neuroanatomical substrates , such as the VTA .
URI: http : / /hdl .handle .net /2152 .3 /66
Date: 2006-12-19

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Role of the ventral tegmental area, cannabinoid receptors and GABA neurons in motor activity. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /66 .

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