Opioid δ agonists and endogenous enkephalins induce different emotional reactivity than μ agonists after injection in the rat ventral tegmental area

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Abstract
The possible role of opioid receptor heterogeneity in the biphasic changes in locomotion (activation and inhibition) induced by non-selective opiates such as morphine, has been investigated by measuring the behaviour of rats exposed to different environments after injection into the ventral tegmental area, of selective μ (DAGO) or δ (DTLET, DSTBULET, BUBU) opioid agonists and of kelatorphan, a complete inhibitor of enkephalin metabolism. δ agonists or kelatorphan-induced hyperactivity in a familiar (actimeter), unfamiliar (four-hole box) and a fear inducing (open-field) environment. These effects were suppressed by naloxone and δ selective antagonists (ICI 174, 864 2 mg/kg SC, naltrindole 7 nmol in the ventral tegmental area). Moreover, the δ agonists and endogenous enkephalins protected by kelatorphan did not affect the emotional state of rats measured in an elevated plus maze. Infused into the ventral tegmental area, DAGO also enhanced locomotion in the actimeter but in contrast to δ agonists and kelatorphan, the μ agonist decreased activity in the open-field and the four-hole box. The hypoactivity observed in these tests could be related to an enhanced emotionality produced by μ receptor stimulation, as shown by the significant decrease in the number of visits and time spent in open arms of the elevated plus maze. Naloxone (0.3 mg/kg SC) but not δ selective antagonists, blocked the various responses induced by DAGO.