Noradrenergic modulation of 4-aminopyridine-induced acetylcholine release from rat cerebral cortex

The noradrenergic influence on cortical acetylcholine (ACh) release was investigated by the cortical cup technique in urethane anaestetized rats treated with 4-aminopyridine (4-AP). The following results were obtained: 1) The increase in ACh release induced by 4-AP (3 mg/kg i.p.) was strongly potentiated by pretreatment with -methyl-p-tyrosine (alpha-MPT) which inhibits catecholamine biosynthesis or by N-(2-chloroethyl)-N-ethyl-bromobenzylamine (DSP4) bringing about a selective degeneration of noradrenergic fibres. Neither pretreatment enhanced the spontaneous ACh output. 2) Pretreatment with p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, did not modify 4-AP effect on ACh output. 3) The alpha blockers, yohimbine (1 mg/kg i.p.) and prazosin (4 mg/kg i.p.), did not enhance the 4-AP effect on ACh release but only delayed its onset. 4) Yohimbine (7 mg/kg i.p.) completely reversed 4-AP effect on ACh release which was significantly decreased. It is concluded therefore that pretreatments with alpha-MPT and DSP4 remove an inhibitory noradrenergic control on cortical ACh release. On the other hand, the alpha blockers might interfere with the ionic mechanisms underlaying the 4-AP effect thus, masking the removal of the noradrenergic control, due to an alpha blockade.