Abstract

A major goal for research on brain stimulation reward (BSR) is the identification of the directly-activated ("first-stage") neurons subserving the powerfully rewarding effect produced by electrical stimulation of the medial forebrain bundle (MFB). This objective was addressed by combining immunohistochemical, lesion, and behavioral methods. Immunohistochemical staining of the immediate early gene product, Fos, was used to visualize neurons activated by rewarding stimulation of the lateral hypothalamic (LH) level of the MFB. Production of Fos protein was increased ipsilateral to the stimulation electrode in subjects that had previously self-stimulated. Among the caudal diencephalic, midbrain and hindbrain structures with pronounced increases in Fos-like immunoreactivity ipsilateral to the site of stimulation were the arcuate nucleus, ventral tegmental area (VTA), central gray, pedunculopontine area (PPTg), parabrachial nucleus, and locus coeruleus. Among the forebrain structures showing a greater density of labeled neurons ipsilateral to the stimulating electrode were the septum, bed nucleus of the stria terminalis (BST), medial preoptic area (MPO), substantia innominata (SI), lateral preoptic area (LPO), and LH. Several of these structures, the VTA, PPTg, LPO, SI, and LH, have been implicated in MFB self-stimulation by the results of pharmacological, psychophysical, electrophysiological, and lesion studies. To complement previous lesion studies implicating the LPO, SI, and LH in BSR, changes in selfstimulation of the LH and VTA were assessed following excitotoxic lesions of more medial structures, including the MPO and BST. Damage centered in the MEW had little or no effect on the rewarding efficacy of more caudal stimulation. Thus, neurons with cell bodies in the medial portion of the basal forebrain may make a smaller contribution to the rewarding effect of MFB stimulation than neurons in the lateral portion. To further probe the role that basal forebrain neurons play in self-stimulation I describe and test an extension of the matching law to relate behavioral performance to the intensity and rate of reinforcement. Analyzing performance in this three-dimensional space provides a means of distinguishing lesion-induced changes that are due to damage in the first-stage neurons and/or their efferents from changes that result from damage in neurons that modulate the rewarding effect of the stimulation.