The effects of D-ala2, D-Leu5-enkephalin injections into the nucleus accumbens on the motility of rats.

Previous studies suggested that the nucleus accumbens (ACB) is relevant for mediating morphine-induced akinesia and catalepsy. In the present study, the effects of unilateral injections of D-ala2, D-leu5-enkephalin (DADL) into the ACB were evaluated. Compared with saline-injected controls, 0.1 and 0.4 nmoles of DADL did not produce any alteration in locomotor activity. One nmol produced a locomotor stimulation, the maximum of which occurred with a delay of about 45 min. In contrast, 4 and 13 nmoles of DADL immediately produced an akinesia, followed by a locomotor stimulation, which was more pronounced after 13 than after 4 nmoles and showed a plateau between 45 and 75 min. Co-administration of naloxone (13 nmoles) did not prevent the initial akinesia, produced by 13 nmoles of DADL, but partly antagonized locomotor stimulation and catalepsy. The results showed that unilateral injections of DADL into the ACB produced a depression of locomotor activity, followed by a stimulation. Both effects showed differences in the dose-dependence. The locomotor stimulation is probably not due to a counter-regulation against the locomotor depression. Studies of Andén and Johnels (1) and of Jones et al (2) suggested that the locomotor activity of rats is critically dependent on the dopaminergic neurotransmission in the nucleus accumbens (ACB). In this area, a remarkable density of opioid receptors has been found (3), in particular of binding sites of 125J-labelled DADL, a ligand, which is a relatively selective marker of opioid receptors of the delta type (4), with a smaller amount of mu-specific binding sites (5). Costall et al. (6) found that bilateral injections of morphine into the ACB produced a catalepsy. In another study, it was found that even unilateral injections of morphine into this area could produce catalepsy and akinesia (7), an effect, which was antagonized by systemic administration of naloxone. It seemed of interest to study the effect of D-ala2, D-leu5-enkephalin (DADL), when injected into the ACB, on locomotor activity.