title: Noradrenergic modulation of evoked dopamine release and pH shift in the mouse dorsal hippocampus and ventral striatum.
abstract: 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 α2adrenergic 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 α2Cadrenoceptor subtype antagonism, but was not affected by or α2Aadrenoceptor 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 α2C,but not α2Aadrenoceptors regulate endogenous dopaminergic activity. We believe our findings hold implications for understanding the efficacy of α2adrenergic agonists and antagonists that are used widely for therapeutic purposes.
authors.affiliation: Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, Japan.
authors.forename: Adam Z
authors.initials: AZ
authors.lastname: Weitemier
authors.affiliation: Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, Japan; Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan. Electronic address: tjmchugh@brain.riken.jp.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McHugh
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D066328:Ventral Striatum / Q000187:drug effects / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D050484:Norepinephrine Plasma Membrane Transport Proteins; D018341:Receptors, Adrenergic, alpha-2; D050486:Serotonin Plasma Membrane Transport Proteins; D004298:Dopamine; D009638:Norepinephrine
keywords: Adrenergic; Alpha 2c; Cerebral blood flow; Hippocampal; Nucleus accumbens; Voltammetry