GABAergic mechanism in histamine H 3 receptor inhibition of K + -evoked release of acetylcholine from rat cortex in vivo

Interactions between histaminergic and cholinergic systems in learning and memory

“…1). Histamine activates cortical H 3 receptors, which are likely localized on GABA interneurons, and inhibits the release of cortical ACh through a GABAergic mechanism [14,48,50]. On the other hand, histaminergic projections to NBM exert a tonic influence on cortical cholinergic activity, depolarizing cholinergic cell bodies through activation of H 1 receptors [22,70], thus increasing ACh release from the cortex [22].…”

“…Recent microdialysis experiments demonstrated that bicuculline, a GABA A receptor antagonist, reversed the inhibition of ACh release induced by immepip, an H 3 receptor agonist, thus suggesting a GABAergic involve-ment [48] [14] increased 100 mM potassiumevoked release of GABA from the cortex of freely moving rats by more than 50% [48]. Thus it is conceivable that H 3 receptors, localized postsynaptically on intrinsic perikarya, facilitated GABA release, which, in turn, inhibited ACh release.…”

“…Although, mechanisms concomitant to H 1 receptor activation cannot be excluded, both electrophysiological and biochemical findings indicate that histamine in the NBM facilitates the cortical cholinergic activity, and strongly suggest that H 1 receptor activation is, at least in part, responsible for this effect. The dual effect of histamine on cortical cholinergic activity, excitatory at the level of NBM cell bodies, and inhibitory at the level of cholinergic terminals [14,48], may have implications for the treatment of disorders associated with impaired cortical cholinergic functions.…”

Acetylcholine, Histamine, and Cognition: Two Sides of the Same Coin

“…H 3 receptor-induced inhibition of cortical ACh is abolished in cortices in which the traffic of action potentials was blocked by tetrodotoxin (Blandina et al 1996), thus strongly suggesting that H 3 receptors modulating cortical ACh release are located postsynaptically on intrinsic perikarya (Arrang et al 1995). Microdialysis experiments demonstrated that immepip, an H 3 receptor agonist, increases GABA release from the cortex of freely moving rats, and bicuculline, a GABAA receptor antagonist, reverses the inhibition of ACh release induced by immepip (Giorgetti et al 1997). Thus, it is conceivable that H 3 heteroreceptors facilitate GABA release, which, in turn, inhibit ACh release.…”

Histamine H3Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata

“…Regions that express H 3 R mRNA and project to the SNr include the striatum, subthalamic nucleus, and raphe nuclei but not the dopaminergic neurons in the substantia nigra pars compacta (SNc)-ventral tegmental area (Pillot et al, 2002). The H 3 R is predominantly a presynaptic receptor that has been shown to inhibit release of HA (Arrang et al, 1983), glutamate (Brown and Reymann, 1996;Brown and Haas, 1999;Molina-Hernandez et al, 2001), GABA (Garcia et al, 1997;Yamamoto et al, 1997;Arias-Montano et al, 2001), norepinephrine (Schlicker et al, 1989(Schlicker et al, , 1992(Schlicker et al, , 1999, dopamine (DA) (Schlicker et al, 1993), acetylcholine (Arrang et al, 1995;Giorgetti et al, 1997;Prast et al, 1999), and 5-hydroxytryptamine (5-HT) in cortex (Schlicker et al, 1988;Fink et al, 1990). The present study was designed to elucidate the role of H 3 receptors (H 3 Rs) in the SNr.…”