Search

A recent report showed that morphine inhibited [3H]clonidine binding to human platelet alpha 2 receptors. As the analgesic effects of morphine and clonidine are clinically additive, we investigated the possibility that morphine might stimulate alpha 2 receptors or alpha 2 mechanisms in rat locus coeruleus (LC) slices. Stimulated LC noradrenaline efflux was measured by fast cyclic voltammetry. Cumulatively applied morphine 10(-8)-10(-4) mol litre-1 had no effect on noradrenaline efflux evoked by pseudo-single-pulse stimulations (20 pulses at 100 Hz) while the alpha 2 agonist dexmedetomidine 2 x 10(-10)-10(-7) mol litre-1 decreased efflux of noradrenaline in a concentration-dependent manner. Administration of single concentrations of morphine 10(-6)-10(-4) mol litre-1 significantly decreased efflux of noradrenaline (by 22% and 17%, respectively) and attenuated the effect of dexmedetomidine in a concentration-dependent fashion. Morphine 10(-6)-10(-4) mol litre-1 also decreased efflux of noradrenaline on long stimulus trains (50 pulses at 50 Hz). These data suggest that the analgesic potentiation of alpha 2 and opioid agonists is not mediated via LC alpha 2 receptors.

We have examined the effects of the highly selective alpha 2-adrenoceptor agonist, dexmedetomidine, on noradrenaline release and cell firing in isolated, superfused slices of rat locus coeruleus. Dexmedetomidine decreased both noradrenaline release and cell firing rate in a concentration-dependent fashion, with an EC50 of 3.97 (SEM 0.97) x 10(-9) mol litre-1 for noradrenaline release and 0.92 (0.53) x 10(-9) mol litre-1 for unit activity. Both effects were reversed completely by the selective alpha 2 antagonist, atipamezole 10(-6) mol litre-1. These results suggest that cell firing and noradrenaline release are under alpha 2 receptor control and that dexmedetomidine potently stimulates these receptors. We conclude that these effects are consistent with the locus coeruleus being a major site of action of the hypnotic anaesthetic alpha 2 agonists.

Fast cyclic voltammetry (FCV) was applied to the detection of stimulated noradrenaline (NA) efflux in the bed nucleus of stria terminalis (BSTV) of the superfused rat brain slice from rats of different ages. Three age groups were compared: young (5 weeks; 130 +/- 8 g), adult (12 weeks; 308 +/- 12 g), and mature rats (36 weeks; 575 +/- 21 g). The effect of train duration (20-99 pulses at 100 Hz) and frequency of stimulation (50 pulses at 10-500 Hz) on NA efflux were examined. The effect of the alpha 2 antagonist yohimbine (1 microM) was also investigated. NA efflux was significantly (p < 0.05) greater in young than adult or mature rats on all train durations and stimulus frequencies tested: Maximal NA efflux on the longest train (99 pulses, 100 Hz, 10 mA, 0.2 ms) was 423 +/- 48 nM (young), 135 +/- 24 nM (adult), and 155 +/- 26 nM (mature). There were no significant differences between adult and mature rats. Yohimbine (1 microM) elevated NA efflux to a greater extent at lower (10 & 20 Hz) than higher frequencies in all age groups. Yohimbine also potentiated NA efflux more (p < 0.05) in young and adult rats than in mature animals. There were no significant differences between young and adult rats. The results indicate early maturational differences in both NA efflux and its control by alpha 2 adrenoceptors. Interestingly, the decreases in NA efflux and in yohimbine response were not temporally linked.