MEDIAL FOREBRAIN-BUNDLE LESIONS FAIL TO STRUCTURALLY AND FUNCTIONALLYDISCONNECT THE VENTRAL TEGMENTAL AREA FROM MANY IPSILATERAL FOREBRAINNUCLEI - IMPLICATIONS FOR THE NEURAL SUBSTRATE OF BRAIN-STIMULATION REWARD

Lesions in the medial forebrain bundle rostral to a stimulating electr ode have variable effects on the rewarding efficacy of self-stimulatio n. We attempted to account for this variability by measuring the anato mical and functional effects of electrolytic lesions at the level of t he lateral hypothalamus (LH) and by correlating these effects to postl esion changes in threshold pulse frequency (pps) for self-stimulation in the ventral tegmental area (VTA). We implanted True Blue in the VTA and compared cell labeling patterns in forebrain regions of intact an d lesioned animals. We also compared stimulation-induced regional [C-1 4]deoxyglucose (DG) accumulation patterns in the forebrains of intact and lesioned animals. As expected, postlesion threshold shifts varied: threshold pps remained the same or decreased in eight animals, increa sed by small but significant amounts in three rats, and increased subs tantially in six subjects. Unexpectedly, LH lesions did not anatomical ly or functionally disconnect all forebrain nuclei from the VTA. Most septal and preoptic regions contained equivalent levels of True Blue l abel in intact and lesioned animals. In both intact and lesioned group s, VTA stimulation increased metabolic activity in the fundus of the s triatum (FS), the nucleus of the diagonal band, and the medial preopti c area. On the other hand, True Blue labeling demonstrated anatomical disconnection of the accumbens, FS, substantia innominata/magnocellula r preoptic nucleus (SI/MA), and bed nucleus of the stria terminalis. [ C-14]DG autoradiography indicated functional disconnection of the late ral preoptic area and SI/MA. Correlations between patterns of True Blu e labeling or [C-14]deoxyglucose accumulation and postlesion shifts in threshold pulse frequency were weak and generally negative. These dir ect measures of connectivity concord with the behavioral measures in s uggesting a diffuse net-like connection between forebrain nuclei and t he VTA.