PharmacoloL,y Biochemistry & Behavior, Vol. 18, pp. 51-54, 1983. Printed in the U.S.A. Reversal of Morphine-Induced Catalepsy by Naloxone Microinjections into Brain Regions with High Opiate Receptor Binding: A Preliminary Report RICHARD E. "WILCOX,* MICHAEL BOZARTH? AND ROBERT A. LEVITT$ *Department of Pharmacology and Toxicology, Alcohol and Drug Abuse Research Program College of Pharmacy, University of Texas at Austin, Austin, TX 78712 ?Department of Psychology, Concordia University, Montreal, Quebec" H3G 1M8 and 5;Department of Psychology, University of Alabama, Birmingham, AL 35294 Received 15 March 1982 WILCOX, R. E., M. BOZARTH AND R. A. LEVITT. Reversalof morphine-induced catalepsy by naloxone microinjec- ?ions into brain regions withhigh opiate receptor binding: A prelirninar3'report. PHARMACOL BIOCHEM BEHAV 18(1) 51-54, 1983.--The relationship between opiate binding density and morphine-induced catalepsy was estimated via dose- response analysis of the brain sites in which naloxone microinjections reversed the catalepsy induced by intraperitoneal morphine. One-hundred forty-one experimentally naive male Long-Evans rats were implanted with chemical microinjec- tion guide cannulae aimed for various high-to-moderate binding density areas within caudate nucleus, central gray matter, thalamus, hypothalamus, amygdala, and frontal cortex as well as low density sites in pyriform cortex and various fiber tracts. Overall, 48 out of 91 animals microinjected with naloxone in brain sites having high-to-moderate density of opiate binding showed reversal of the cataleptic response. Dose-response effects were found in all 6 high-to-moderate density sites: ranging from 85% reversals at 100 mcg naloxone over all sites to 34%.reversals at 0.01 mcg naloxone. There were no reversals out of 38 naloxone microinjection in brain sites having a low density of opiate binding and no reversals out of 18 saline microinjections in either high-to-moderate or low opiate binding density loci. These results suggest a role for limbic and basal ganglia portions of the opiate system in a motor aspect of narcotic action. We speculate that these loci may also play a role in the motor expression of the response to the analgesic and euphoric actions of morphine to supplement actions mediated through periventricular structures. Catalepsy Morphine Opiate receptor Naloxone Motor system Frontal cortex Caudate nucleus Thalamus Hypothalamus Amygdala Periaqueductal gray matter THE reports demonstrating stereospecific, high affinity binding of opiate drugs to subcellular fractions from tissue from several regions of mammalian brain [6,15] provided an important tool with which to probe the neuroanatomical subs?rate of the actions of morphine [9]. In several species the highest concentrations of such ligand-binding defined opiate receptors are found in limbic system and basal ganglia loci. An especially rich distribution is found in a group of periventricular core structures including periaqueductal gray, midbrain reticular formation, and medial hypothalamus and thalamus, comprising a spinoreticularpaleospi- nothalamic system implicated in the processing of nociceptive information [6,10]. An important focus of re- search on opioid drugs is the separability of the various ac- tions of morphine with a goal of developing a narcotic anal- gesic with reduced potential for self-administration, tolerance development and physical dependence [l I]. One useful approach for determining the neuroanatomical sub- strate for opioid actions has been the correlation between microinjections of narcotic agonists or antagonists into spe- cific brain loci with behavior [5, 8, 17, 22]. A potential limitation of early work on the neural sub- strate for narcotic actions is that narcotic analgesics have a profound influence on general sensorimotor processing in addition to their analgesic-euphoric effects [1,20]. Further- more, as commonly measured, analgesia and physical de- pendence induced by morphine involve changes in the motor output of the organism [5, 23, 24]. A clarifcation of the brain areas participating in opiate-induced changes in general sen- sorimotor function may help to separate these responses from analgesia-euphoria and dependence. Previous studies have implicated structures such as the caudate nucleus in the rigidity [4] catalepsy [24] but not the analgesia [20] associated with morphine administration. The Copyright © 1983 ANKHO International Inc.--0091-3057/83/010051-04503.00/0