Effect of opiate receptor agonists on striatally-mediated head turning: An [formula omitted] model of opiate delta receptor activation?

Abstract

Electrical stimulation of the striatum in conscious rats elicits a contralateral head-turn. Modification of this response by opiate drugs injected sub-cutaneously or into the ipsilateral globus pallidus has been investigated. Morphine, normorphine and ethylketocyclazocine had no effect on the head-turn latency but met-enkephalin and D-Ala 2, D-Leu 5-enkephalin, injected into the pallidum, and small doses of etorphine injected subcutaneously, produced a dose-related slowing of the response. Large doses of the opiate receptor antagonist naloxone antagonised the effect of etorphine. These results suggest the presence of opiate delta receptors in the rat globus pallidus and this model may therefore prove useful for studying the effects of other agents acting at the delta receptor. Following the work of Martin, Eades, Thompson, Huppler and Gilbert, 1976 and Lord, Waterfield, Hughes and Kosterlitz, 1977, it is now generally accepted that there are multiple opiate receptors which can be characterised by their response to a range of agonists and by the effectiveness of antagonists in reversing some of these actions. However, although mu, kappa and sigma opiate effects can be measured in vivo (Martin et al., 1976), there is no published model for studying effects at the opiate delta-receptor in vivo . In the search for such a model, a number of opiate agonist drugs were evaluated in the striatally-evoked head-turn model described by Slater, Lee, Longman and Crossman (1980). This model was thought to be particularly appropriate because of the proposed existence of a striopallidal enkephalin pathway in the rat brain (Cuello and Paxinos, 1978) and the demonstration of the release of enkephalin from slices of rat globus pallidus in vitro (Iversen, Iversen, Bloom, Vargo and Guilleman, 1978) and from cat globus pallidus in vivo (Cesselin, Soubrie, Bourgoin, Artaud, Reisine, Michelot, Glowinski and Hamon, 1981). However, in contrast to the findings reported by Slater and Longman (1980), the results of the present study demonstrate that a slowing of the head turn response was specifically produced by opiate delta-receptor agonist compounds and that this effect was abolished by large doses of naloxone.