b-endorphin is an endogenous opioid peptide that has been hypothesized to be involved in the behavioral effects of drugs of abuse including psychostimulants. Using microdialysis, we studied the effect of cocaine on extracellular levels of b-endorphin in the nucleus accumbens, a brain region involved in the reinforcing effects of psychostimulant drugs. Experimenter-delivered cocaine (2 mg/kg, i.v.) increased extracellular b-endorphin immunoreactive levels in the nucleus accumbens, an effect attenuated by 6-hydroxy-dopamine lesions or systemic administration of the D 1 -like receptor antagonist, SCH-23390 (0.25 mg/kg, i.p.). The effect of cocaine on b-endorphin release in the nucleus accumbens was mimicked by a local perfusion of dopamine (5 lM) and was blocked by coadministration of SCH-23390 (10 lM).Self-administered cocaine (1 mg/kg/infusion, i.v.) also increased extracellular b-endorphin levels in the nucleus accumbens. In addition, using functional magnetic resonance imaging, we found that cocaine (1 mg/kg, i.v.) increases regional brain activity in the nucleus accumbens and arcuate nucleus. We demonstrate an increase in b-endorphin release in the nucleus accumbens following experimenter-delivered and self-administered cocaine mediated by the local dopaminergic system. These findings suggest that activation of the b-endorphin neurons within the arcuate nucleus-nucleus accumbens pathway may be important in the neurobiological mechanisms underlying the behavioral effects of cocaine.

Evidence is emerging for significant inter-hemispheric cortical plasticity in humans, opening important questions about the significance and mechanism for this long range plasticity. In this work, peripheral nerve deafferentation was performed on both the rat forepaw and hindpaw and cortical reorganization was assessed using functional MRI (fMRI). Sensory stimulation of the forepaw or the hindpaw in rats that experienced only partial denervation resulted in activation in only the appropriate, contralateral, primary somatosensory cortex (SI). However, 2-3 weeks following complete denervation of the rats' forepaw or hindpaw, stimulation of the intact paw resulted in fMRI activation of ipsilateral as well as contralateral SI. To address whether inter-cortical communication is required for this cortical reorganization, the healthy hindpaw SI representation was stereotaxically lesioned in rats which had the other hindpaw denervated. No fMRI activation was detected in the ipsilateral SI cortex after lesioning of the contralateral cortex. These results indicate that extensive inter-hemispheric cortical-cortical reorganization can occur in the rodent brain after peripheral nerve deafferentation and that cortical-cortical connections play a role in mediating this inter-hemispheric cortical reorganization.

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