Brain Research, 149 (1978) 223-228 223 © Elsevier/North-Holland BiomedicalPress Enkephalin-containing pathway: amygdaloid efferents in the stria terminalis GEORGE R. UHL, MICHAEL J. KUHAR and SOLOMONH. SNYDER* Departments of Pharmacology and Experimental Therapeutics and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md. 21205 (U.S.A.) (Accepted December29th, 1977) Several lines of evidence suggest an association of the opioid pentapeptides methionine-enkephalin (met-enkephalin) and leucine-enkephalin (leu-enkephalin)10,16 with the stria terminalis, the amygdala and the interstitial nucleus of the stria terminalis. Biochemicalla,17 and autoradiographic studies reveal densities of opiate receptors in the interstitial nucleus of the stria terminalis and in the amygdala 1. Enkephalin-positive cells9, fibers and terminalsS, is are concentrated in the central nucleus of the amygdala and in the interstitial nucleus of the stria terminalisS, is. DeOlmos noted that the ventro- lateral portion of the stria terminalis carries fibers arising from cell bodies in the central, lateral and basolateral arnygdaloid nuclei that terminate 'almost exclusively' in the lateral portion of the interstitial nucleus of the stria terminalis5 (Fig. 1). We now present evidence for an amygdalofugal enkephalin-containing neuronal pathway arising from amygdaloid cells and running through the ventrolateral stria terminalis. Specific antisera to met-enkephalin and leu-enkephalin with negligible cross- reactivity by radioimmunoassay with a- and fl-endorphins and other peptides were obtained from rabbits as described elsewhere 3. Each antiserum possesses more than 200-fold greater affinity for the enkephalin pentapeptide against which it was directed than for the other pentapeptide. Normal 100 g Sprague-Dawley rats or rats preinjected in the lateral ventricle with 50/,g colchicine in 25/zl 0.9 % NaC148 h before sacrifice~0 were used in these studies. Electrolytic lesions of the amygdala in 9 animals employed a Grass radiofrequency lesion maker and a stainless-steel needle electrode, insulated except for approximately 0.5 mm from the tip with multiple layers of spray varnish. Eight mA of current were passed through this electrode for 30 see at stereotaxic co- ordinates anterior 5.5 mm (measured from bregma), lateral 3.7 mm (measured from the midline), and deep 7.0 mm (measured from the pial surface) of pentobarbital-anesthet- ized, 150-220 g rats held in a standard stereotaxic frame (David Kopf). In 6 rats, stria terminalis cuts were made stereotaxically by passing a No. 11 knife blade in a frontal plane from 1.5 to 5 mm lateral to the midline, at depths of 4-5.5 mm from the pial sur- face. Cuts were made from approximately 3.8 to 5.0 mm anterior to the ear bars. Con- * To whomcorrespondenceshouldbe sent.