Pharmacoh~gy Biochemisto' & Behavior. Vol. I1. pp. 505-511. Printed in the U.S.A. Exploratory Behaviour and Aversive Thresholds Following Intra-Amygdaloid Application of Opiates in Rats R. J. RODGERS S~'hool of Psychology, University of Bradfi~rd, Bradford, UK and SANDRA E. FILE Department oJ'Pharmacology, The School of Pharmacy, University of London, UK Received 16 July 1979 RODGERS, R. J. AND S. E. FI L E. E~ploratoo' behai'iourand at'er.~irethreshohls fi,lhm'ing intra-amygdaloidapplit'ation o.(opiates in rats. PHARMAC. BIOCHEM. BEHAV. i1(5) 505-511, 1979.--Rats were bilaterally implanted with guide cannulae aimed at the central or medial nucleus of the amygdala. Microinjections of morphine (10ptg) at both sites significantly elevated the threshold of response in the flinch-jump test: but only at medial sites did naloxone (l~g) antagonise this effect. However, in the hole-board test. an opposite pattern of results emerged. Morphine injections into the central nucleus produced naloxone-reversible reductions in both exploration and activity whilst, in the medial nucleus, the morphine-induced decrease in exploration was not reversed by naloxone. It is concluded that (I) the presence or absence of naloxone-sensitive opiate receptors cannot always be deduced on the basis of a single behavioural test and (2) within the amygdaloid complex, two distinct naloxone-sensitive opiate systems appear to be involved in the modulation of be- havioural responses to different forms of stimulation. Morphine Naloxonc Aversive thresholds Exploration Motor activity Central amygdala Medial amygdala WITHIN the past decade, considerable advances have been made in our understanding of the central sites at which the opiates exert their potent behavioural effects (1351-for re- view). Specific opiate binding sites and natural ligands (enkephalins/endorphins) have been located at levels from the spinal cord through the midbrain to various forebrain structures [2, 3, 4, 21, 26, 31, 33] . Strong analgesic re- sponses have been produced by microinjection of morphine in spinal cord I341 and midbrain [18, 27, 28, 361 areas. Con- sequently, it has been argued that the analgesic effectiveness of morphine relates to its ability to mimic endogenous ligands at these sites. Such suggestions are supported by the findings that both brain-stimulation analgesia [I, 161 and acupuncture analgesia 1181 are blocked by opiate an- tagonists. However, it is perhaps misleading to consider this endogenous system as functioning only in relation to pain mechanisms. Indeed, a general role for these peptides in the mediation of stress responding has recently been proposed 129[. More specifically, several studies have argued for the involvement of the endogenous opiate system in exploration [121, sexual behaviour [6,201, social affect [14. 221 and men- tal illness [30]. In this context, it should be noted that very high densities of opiate receptors and ligands are found in regions outside classical pain pathways. One such area is the amygdaloid complex [4], a subcortical structure more tradi- tionally associated with limbic regulation of affective be- haviour. Affective responses to aversive stimulation are strongly inhibited by lesions of the medial amygdala [151, an effect that has been equated with the action of narcotic analgesics [7]. Recent results from our own laboratory support these findings. Microinjection of morphine into this limbic area, whilst ineffective in altering non-emotive spinal reflexes to pain, produced naloxone-reversible elevations in the more emotive jump response to electric shock [24, 25]. This profile suggested that a possible function of the amygdaloid opiate system may be to decrease affective responding in stressful situations. To investigate further the possible behavioural signifi- cance of the amygdaloid opiate system(s), the current study examined the effects of intra-amygdaloid opiate injections on two behavioural tests: responses to a novel environment (hole-board test) and reactivity to electric shock (flinch- jump test). Two injection sites within the amygdaloid com- plex (central and medial nuclei) were chosen on the basis of differential opiate receptor and peptide distribution [4, 26, 31,321. Copyright ('~ 1979 ANKHO International Inc.--0091-3057/79/110505-07501.20/0