In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

Abstract

Cholinergic neurons in the nucleus accumbens contain GABAA and GABAB receptors that are thought to inhibit neural activity. We analyzed the roles of GABAA and GABAB receptors in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. The effects of GABA receptor ligands on the accumbal dopamine efflux were also analyzed because accumbal cholinergic and dopaminergic neurons could mutually interact. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 30–60 min infusions. To monitor basal acetylcholine, a low concentration of physostigmine (50 nM) was added to the perfusate. GABAA receptor agonist muscimol (3 and 30 pmol) induced a dose‐related decrease in accumbal acetylcholine. GABAB receptor agonist baclofen (30 and 300 pmol) also produced a dose‐related decrease in acetylcholine. GABAA receptor antagonist bicuculline (60 pmol) which failed to alter baseline acetylcholine counteracted the muscimol (30 pmol)‐induced decrease in acetylcholine. GABAB receptor antagonist 2‐hydroxysaclofen (12 nmol) which failed to change baseline acetylcholine, counteracted the baclofen (300 pmol)‐induced decrease in acetylcholine. Neither muscimol (30 pmol) nor baclofen (300 pmol) which reduced accumbal acetylcholine altered baseline accumbal dopamine. Neither bicuculline (60 pmol) nor 2‐hydroxysaclofen (12 nmol) also affected the baseline dopamine. These results show that GABAA and GABAB receptors each exert inhibitory roles in the regulation of accumbal cholinergic neural activity. The present results also provides in vivo neurochemical evidence that stimulation of GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.

Modulation of stimulated dopamine release in rat nucleus accumbens shell by GABA in vitro: Effect of sub‐chronic phencyclidine pretreatment

“…It is also worth noting that DHβE did not reverse the effect of baclofen either, so is unlikely to contribute to the GABA‐B‐mediated effect. This is agreement with other studies showing that the attenuation of dopamine release by either muscimol or baclofen was not disrupted by co‐application of a nicotinic antagonist (Lopes et al., 2019; Pitman et al., 2014), but is at odds with the recent report of muscimol and baclofen causing a dose‐dependent increase in acetylcholine release in NAc in vivo , albeit that this was not accompanied by changes in dopamine (Aono et al., 2019). This may be due to the presence of “long‐loop” networks in vivo , although we cannot rule out differences in local functionality between in vitro and in vivo preparations.…”

Adolescence as a critical period for nandrolone‐induced muscular strength in relation to abuse liability, alone and in conjunction with morphine, using accumbal dopamine efflux in freely moving rats

“…Based on previously described procedures for our online in vivo microdialysis technique (Aono et al, 2017(Aono et al, , 2019Kiguchi et al, 2016;Watanabe et al, 2018), dialysis and neurochemical measurements were carried out as follows:…”

Neuroplasticity and Multilevel System of Connections Determine the Integrative Role of Nucleus Accumbens in the Brain Reward System

“…Besides inhibition of DA release, GABA also exerts an inhibitory effect upon acetyl-cholinergic interneurons in NAc, via its interaction with GABAARs and GABABRs [107]. Stimulation of these receptors in cholinergic neurons in NAc results in a reduction of acetylcholine efflux [108]. Considering that the DA release in NAc from the axonal terminals of the VTA neurons is under the simultaneous control of the GABA-ergic (release inhibition) and cholinergic (release stimulation) systems, an appropriate level of activation of the cholinergic interneurons is required for DA release in NAc to balance the inhibitory effect of the GABA-ergic system and maintain the DA concentration at a level sufficient for the physiological functions of NAc [109].…”