ABSTRACT
CB1R play a role in alcohol withdrawal and in some effects of acupuncture. Interestingly, acupuncture has been used to alleviate alcohol withdrawal. Here, we investigated electroacupuncture (EA) effects during ethanol withdrawal on CB1R immunoreactivity. Male Swiss mice were daily injected with ethanol (2g/kg, i.p) (EtOH group), for 21 days. EA was performed daily during 4 days of ethanol withdrawal. The stimuli of 2 or 100 Hz were provided in two acupoints combination: Ea1 [(ST-36/Zusanli) and (PC-6/Neiguan)] or Ea2 [(DU-14/Dazhui) and (DU-20/Baihui)]. The specificity of the acupoints were assessed by the inclusion of three additional groups, Ea3 [(ST 25/Tianshu - acupoints used to other non-related disorders)], Sham1 and Sham2 (transdermic stimulation nearly to the respective acupoints). EtOH group were only handled during withdrawal and Saline group was chronically treated with Saline and handled similarly to EtOH group. One day after withdrawal the animals were perfused and their brains processed for immunohistochemistry. There was an increase of CB1R in the prefrontal cortex, striatum, hippocampus, amygdala and ventral tegmental area. The procedures used in the 2HzEa1 and 100HzEa2 groups were the most effective and specific to inhibit this CB1R upregulation. Therefore, EA inhibits CB1R upregulation seen in ethanol withdrawn mice. The specificity of acupoints stimulation depends of the encephalic nuclei, acupoints association and frequency of stimulation.
Subject(s)
Central Nervous System Depressants/adverse effects , Electroacupuncture , Ethanol/adverse effects , Receptor, Cannabinoid, CB1/physiology , Substance Withdrawal Syndrome/metabolism , Acupuncture Points , Animals , Behavior, Animal/drug effects , Blotting, Western , Brain/pathology , Brain Chemistry , Immunohistochemistry , Male , Mice , Motor Activity/drug effects , Substance Withdrawal Syndrome/pathology , Up-Regulation/physiologyABSTRACT
Extracellular signal-regulated kinase (ERK) plays a role in neuronal changes induced by repeated drug exposure. Given that electroacupuncture reverses locomotor sensitization induced by ethanol, we investigated whether this effect is parallel to ERK signalling. Mice received daily ethanol (2 g/kg i.p), for 21 d. Electroacupuncture was performed daily, during four (subsequent) days of ethanol withdrawal. The stimulus of 2 Hz or 100 Hz was provided in combinations of two acupoints: Ea1 (ST-36/Zusanli and PC-6/Neiguan) or Ea2 (Du-14/Dazhui and Du-20/Baihui). The specificity of acupoint effects were assessed by the inclusion of additional groups: Ea3 (ST-25/Tianshu--acupoint used for other non-related disorders), Sham1 or Sham2 (transdermic stimulation near the respective acupoints). The control group was only handled during withdrawal and the saline group was chronically treated with saline and handled similarly to controls. At day 5 of withdrawal, each group was divided in two subgroups, according to the presence or absence of ethanol challenge. The animals were perfused and their brains processed for pERK immunohistochemistry. Only Ea1 at 100 Hz (Ea1_100) and Ea2 at 2 Hz (Ea2_2) reversed locomotor sensitization induced by ethanol. Ethanol withdrawal decreases pERK in the dorsomedial striatum. This decrease is not abolished by electroacupuncture. Conversely, ethanol challenge increases pERK in the dorsomedial striatum, infralimbic cortex and central nucleus of amygdala. The specificity of acupoint stimulation to reverse these increases was seen only for Ea2_2, in the infralimbic cortex and dorsomedial striatum. Therefore, behavioural effects of Ea2_2 (but not Ea1_100) depend, at least in part, on ERK signalling.
