Regulation of spontaneous acetylcholine release in the hypothalamic vasopressinergic supraoptic nucleus of a freely moving rat: a study by in vivo microdialysis.

We employed a brain microdialysis method to examine the possible regulation of spontaneous acetylcholine (ACh) release in the hypothalamic vasopressinergic supraoptic nucleus (SON) of rats. We monitored the basal ACh release in the SON-microdialysate. The addition of tetrodotoxin (10(-6) M) to the perfusate (saline containing 10(-4) M physostigmine) decreased the basal ACh release. A muscarinic receptor antagonist, atropine (non-selective) or pirenzepine (M1-selective), increased the basal ACh release in a concentration-dependent manner. The maximal increase occurred at 20-40 min after the start of the infusion of antagonists. The ED50 values for the stimulatory effects of atropine and pirenzepine were 9.4 x 10(-8) and approx. 10(-4) M, respectively. The effect of atropine (10(-6) M) was inhibited by simultaneous addition of the muscarinic agonist oxotremorine (10(-5) M). The results showed a negative feedback regulation of the spontaneous ACh release through the activation of muscarinic receptors in the SON. The weak effect of pirenzepine in increasing the ACh release, compared with atropine, suggests that ACh release in the nucleus is mainly regulated by the non-M1-muscarinic receptor subtype.