Noradrenergic modulation of evoked dopamine release and pH shift in the mouse dorsal hippocampus and ventral striatum

Rapid monoamine release in the dorsal hippocampus is not well characterized, despite its postulated role in modulating fast hippocampal circuit dynamics. We measured monoamine release in the dorsal hippocampus upon stimulation of the ventral tegmental area (VTA) with fast-scan cyclic voltammetry in anesthetized norepinephrine-depleted and non-depleted mice. Within the hippocampus, norepinephrine depletion altered the ability of α₂ adrenergic compounds and transporter blockers to modulate the small, evoked monoamine signal. These manipulations also affected the pH shifts observed after stimulation in a drug-dependent manner. The evoked signal was potentiated by α_2C adrenoceptor subtype antagonism, but was not affected by or α_2A adrenoceptor antagonism. The same subtype-specific pattern was observed on evoked dopamine release in the ventral striatum. The pharmacological and anatomical evidence supports a contribution by dopamine to the VTA-evoked hippocampal monoamine signal, and confirms the interaction between the mesohippocampal and coeruleohippocampal systems. These results also reinforce the notion that α_2C, but not α_2A adrenoceptors regulate endogenous dopaminergic activity. We believe our findings hold implications for understanding the efficacy of α₂ adrenergic agonists and antagonists that are used widely for therapeutic purposes.