Real-time monitoring of endogenous noradrenaline release in rat brain slices using fast cyclic voltammetry. 2. Operational characteristics of the α 2 autoreceptor in the bed nucleus of stria terminalis, pars ventralis

Abstract

Fast cyclic voltammetry (FCV) at carbon fibre microelectrodes was used to monitor stimulated noradrenaline (NA) efflux in slices of the ventral part of the rat bed nucleus of stria terminalis (BSTV) superfused with artificial cerebrospinal fluid at 32°C. NA efflux was evoked by local electrical stimulation (trains of 10–50 pulses, 0.2 ms duration, 10 mA constant current at 10–500 Hz). The effects of four α 2 antagonists (yohimbine, rauwolscine, parazosin and WB 4101) and three α 2 agonits (clonidine, oxymetazoline and UK 14304) were examined. All drugs (1 μM) were added via the superfusate. Yohimbine and rauwolscine increased NA efflux on the lower but not the higher frequency trains: maximum increases (on 20 Hz, 50 pulse stimulation) were to 392±63% (yohimbine) and 243±7% (rauwolscine). There was a threshold train duration for demonstration of autoreceptor antagonism of 500–1000 ms. Prazosin and WB 4101 did not increase NA efflux but caused a modest decrease at the higher (100–500 Hz) frequencies. The effects of the α 2 agonists were also affected by stimulus train duration. Longer trains reduced agonist (clonidine) effects. When tested on pseudo-one pulse (POP) stimulations (less than 100 ms duration), the α 2 agonists decreased NA efflux. UK 14304 reduced NA efflux on 20 pulse/200 Hz stimulation to a g reater degree ( 86±7%) than the partial agonists clonidine ( 39±3%) or oxymetazoline ( 40±8%). The present results demonstrate α 2 autoreceptors are a major mechanism in the control of NA efflux in the BSTV. The lack of potentiation of NA efflux by prazosin suggests that the autoreceptor is not of the α 2B or α 2C subtype while the clear inhibitory action of oxymetazoline suggests an α 2A or α 2D receptor. With appropriate selection of stimulation conditions, the actions, of both antagonists and agonists (partial and full) can be examined.