Anxiolytic effects of ethanol are partially related to a reduced expression of adenylyl cyclase 5 but not to μ-opioid receptor activation in rat nucleus accumbens

Abstract

Anxiolytic effects of alcohol participate in the reinforcing properties of the drug, in which nucleus accumbens (NAcc) is implicated. The opioidergic system in NAcc is considered a main pathway involved in the emotional responses of animals: rats microinjected with morphine in NAcc and the systemic administration of μ-opioid receptors (MOR) agonists yield low anxiety scores in the elevated plus maze (EPM), a behavioral test of anxiety. However, the specific participation of NAcc MOR in the anxiolytic effect of ethanol has not been studied. AC5, a cAMP-synthezising adenylyl-cyclase, is highly expressed in NAcc; it is negatively coupled to MOR and has been implicated in anxiety levels of animals. We evaluated the anxiolytic effects of an intra-gastric administration of ethanol (2.5 g/kg) in animals subjected to EPM at 1, 4, and 8 h after drug or water exposure. Locomotion was assayed with the open-field test; we also measured accumbal AC5 and MOR mRNA levels by RT-PCR. After 1 h, ethanol-exposed animals showed anxiolytic-like behavior, as well as decreased and increased AC5 and MOR expression in NAcc, respectively. Intra-accumbal injection of β-funaltrexamine (FNA), a MOR antagonist, did not block ethanol-induced anxiolysis, rather it induced a tendency to increase anxiety levels in the water-exposed group. FNA partially decreased accumbal AC5 expression in ethanol-treated rats. We concluded that AC5 in NAcc is participating in the emotional effects of ethanol; that MOR was not mediating the drug-induced AC5 reduction in NAcc nor the ethanol-induced anxiolysis. MOR only might be involved in basal levels of anxiety of animals.

Roles of the µ-opioid receptor and its related signaling pathways in the pathogenesis of premenstrual syndrome liver-qi stagnation

“…Briefly, the hippocampi were separated under sterile conditions and digested with 0.25% trypsin at 37˚C for 20 min. Following filtering with a 200-mesh filter, the cells were seeded into poly-lysine-coated 6-well plates at a density of 4x10 5 /ml, then cultured in a 37˚C, 5% CO 2 incubator. After 24 h, the cells were incubated at 37˚C with serum-free Neurobasal-A medium (10888-022; Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA), which was replenished every 3 days.…”

“…Increasing evidence indicates that the µ-opioid receptor (MOR) serves a key role in the regulation of mood and emotional disorders (5)(6)(7). In particular, it has been observed that withdrawal of endogenous opioid peptides is associated with the development of PMS, and decreased levels of opioid peptides are considered as a marker of the condition (8)(9)(10)(11)(12)(13).…”

Alcohol effects on synaptic transmission in periaqueductal gray dopamine neurons

“…As such, understanding the actions of acute alcohol exposure is an important area of investigation. Animal studies have shown that acute alcohol exposure can induce locomotor stimulation (Humeniuk, White, & Ong, 1993; Koob, 1992; Kornetsky, Bain, Unterwald, & Lewis, 1988) and is also anxiolytic (Morales-Mulia et al, 2012; Sharko, Kaigler, Fadel, & Wilson, 2013). Alcohol exposure also modifies pain perception and the anti-nociceptive effects of opiates (Peris, Peiro, Hernandez, & de la Parte, 2005).…”

Influence of the hippocampus on amino acid utilizing and cholinergic neurons within the nucleus accumbens is promoted by histamine viaH1receptors

“…However it is not known whether histamine modulates glutamate-mediated responses under in vivo conditions. The NAc is a part of the basal forebrain that seems to participate in emotional processes such as stress response (Abercrombie et al, 1989;Lemos et al, 2012) and anxiety (Morales-Mulia et al, 2012), antipsychotic drug actions (O'Donnell and Grace, 1996), sensorimotor gating (Wan and Swerdlow, 1996), and the pathophysiology of schizophrenia (O'Donnell and Grace, 1998). This aspect of the ventral striatum is innervated by the hippocampal formation via the fornix/fimbria tract (Kelley and Domesick, 1982;Groenewegen et al, 1987).…”