Stimulant effects of enkephalin microinjection into the dopaminergic A10 area

Abstract

THE overt behaviour of various species is affected in different ways by opiate drugs. Mice and cats show behavioural stimulation following a systemic morphine injection whereas rats and dogs generally exhibit decreased behavioural activity^1–4, although in certain conditions, stimulant effects can also be seen in the latter species^4,5. Tatum et al. suggested that there are several distinct sites of action of opiate drugs in brain and that the relative dominance of one system over another determines whether the stimulant or depressant effects predominate⁴. Indeed, direct microinjections of morphine into the ventral tegmental area (VTA) have been shown to result in facilitation of self-stimulation behaviour whereas similar injections into the periaqueductal gray matter cause only an attenuation of this behaviour⁶. The discovery of endogenous ligands for opiate receptors in the brain⁷ has focused attention on the role of these peptides in various aspects of behaviour. Their analgesic properties following intr a ventricular and intracerebral injection are well documented⁸. Recently, it has been reported that infusion of α-endorphin into the substantia nigra induced stereotyped behaviour⁹, whereas local injections into the nucleus accumbens of the long-acting synthetic enkephalin analogue, [D-Ala²]-Met⁵-enkephalinamide (AME), produced an increase in locomotor activity¹⁰. We now report that infusion of AME (0.03–2.0 µg) bilaterally into the dopaminergic (DA) A10 area of the VTA induces a short-latency behavioural stimulant effect reminiscent of effects produced by stimulation of the mesolimbic DA pathway¹¹. This effect is antagonised by pretreatment with the opiate receptor blocker naloxone.