ACTH 1–24 and lysine vasopressin selectively activate dopamine synthesis in frontal cortex

Abstract

The accumulation of [ 3H]catecholamines from [ 3H]tyrosine in frontal cortical, septal, striatal and hippocampal slices was examined following intracerebroventrcular (i.c.v.) injections of ACTH 1−24, lysine vasopressin (LVP) and saline. Both ACTH 1−24 and LVP (1 μg) selectively increased the accumulation of [ 3H]dopamine (DA) in frontal cortical slices, but did not affect that of [ 3H]norepinephrine (NE). LVP but not ACTH 1−24 also inhibited the accumulation of [ 3H]DA in striatal slices. ACTH 1−24 did not alter the accumulation of [ 3H]NE in hippocampal slices, nor did LVP alter the accumulation of either catecholamine (CA) in septal slices. In vitro incubations with ACTH analogs or LVP failed to alter the rate of accumulation of [ 3H]CAs in striatal, substantia nigral and frontal cortical slices, except for an inhibitory effect at high doses. This effect is believed to be an artifact of precursor dilution caused by release of tyrosine following degradation of the peptides. Neither peptide modified the increased [ 3H]CA accumulation stimulated by 26 mM K +, nor did ACTH 1–24 modify the inhibition of [ 3H]CA accumulation caused by 3 × 10 −6 M haloperidol or 3 × 10 −7 M apomorphine. Selective activation of the mesocortical DA system has also been reported to occur in response to footshock, suggesting the possibility that endogenous ACTH and/or LVP might mediate the stress-induced activation of mesocortical DA synthesis. Alternatively, i.c.v. injections of these peptides may themselves be stressful and thus indirectly elicit the response.