Opioid inhibition of rat medial vestibular nucleus neurones in vitro and its dependence on age

Abstract 

Extracellular and whole-cell patch clamp intracellular recordings were made from rat medial vestibular nucleus (MVN) neurones in vitro, and their responses to selective μ-, κ- and δ-opioid receptor agonists and antagonists were examined. Of 127 neurones tested, the large majority were inhibited in a dose-dependent manner by the δ-opioid receptor agonists [d-Ala², d-Leu⁵]-enkephalin (DADLE) and [d-Pen², Pen⁵]-enkephalin (DPLPE). The μ-opioid receptor agonist morphine and the κ-receptor agonist U50,488 did not affect the tonic discharge rate of any of the 63 MVN cells tested. The δ-receptor antagonist naltrindole effectively antagonised the inhibitory effects of DADLE and DPLPE. Weak excitatory responses to high doses of DADLE were seen in only two MVN cells. These results demonstrate the presence of δ- but not μ- or κ-opioid receptors on tonically active MVN neurones. Whole-cell intracellular recordings from MVN cells in a current clamp showed that the DADLE-induced inhibition was accompanied by membrane hyperpolarisation and decrease in input resistance, while voltage clamp experiments showed that DADLE induced an outward membrane current that was reduced but not abolished by 20 mM tetraethylammonium bromide. Thus the mechanisms of action of DADLE in inhibiting MVN cells involve the potentiation of outward K currents, in a similar way to the effects of opioids in other areas of brain. The inhibitory effects of DADLE increased linearly with age, so that the responses to DADLE in the youngest animals used here (60–80 g, approx. 3 weeks of age) were relatively small, increasing significantly over the following 2–3 weeks. This age-dependence may be due to post-natal changes in the density of δ-opiate receptors or the efficacy of the signalling pathways activated by them in the MVN cells over this time.