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Background Hyperalgesia or increased sensitivity to pain is often found in alcoholics during alcohol withdrawal and may contribute to relapse drinking. Alternative therapies such as acupuncture and electroacupuncture ( EA), through mechanisms involving opioid receptors, may reduce pain and substance dependence and withdrawal syndromes. The lateral habenula ( LHb), an epithalamic structure rich in mu opioid receptors ( MORs), is a critical target for both drugs of abuse and pain. We previously observed hyperalgesia in rats withdrawn from chronic ethanol (EtOH) drinking and found that EA at the acupoint Zusanli ( ST36) reduced EtOH intake. This raised question of whether EA can alleviate hyperalgesia during alcohol withdrawal and, if so, whether the mechanism involves MORs in the LHb. Methods We trained male rats to drink EtOH using the intermittent access 20% EtOH 2-bottle free-choice drinking paradigm for 8 weeks, after which the alcohol supply was discontinued. We measured pain sensitivity using radiant heat (a light beam directed at the hind paw of rats) and compared the paw withdrawal latencies ( PWLs) with and without EA at ST36. Results The PWLs were significantly shorter in rats at 24, 48, and 72 hours and 7 days after the discontinuation of EtOH when compared to EtOH-naïve rats. After a single administration of 2-Hz EA for 20 minutes at ST36, the PWLs at 24 hours after the withdrawal of EtOH were significantly greater than those of the sham group (2-Hz EA at the tail). Furthermore, the effect of EA on PWLs was significantly attenuated by bilateral intrahabenula infusion of the MOR antagonist naltrexone. Conclusions These results suggest that EA can alleviate hyperalgesia during EtOH withdrawal through a mechanism involving MORs in the habenula. Based on this, EA could be of potential value as a therapy for hyperalgesia in alcohol dependence. [ABSTRACT FROM AUTHOR]

Background The aversive properties of ethanol (EtOH) that limit its intake are poorly understood. There is an increasing interest in the role of the rostromedial tegmental nucleus ( RMTg), because it encodes aversion signals and inhibits motivated behaviors. It is also a major source of inhibitory GABAergic inputs to the midbrain dopamine neurons. Up to this time, the role of the RMTg in EtOH-drinking behaviors has not been well explored. Methods Male Long-Evans rats were trained either to drink EtOH under the intermittent 2-bottle-choice protocol or to self-administer EtOH in operant chambers under fixed-ratio-3 schedules. Changes in drinking behaviors induced by the bilateral infusion into the RMTg of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ( AMPA), an agonist of AMPA-type glutamate receptors, or muscimol, an agonist of GABAA receptors, were measured. Results Consumption and preference for EtOH, numbers of active lever pressing, and head entrance to the EtOH port were all significantly decreased upon activation of the RMTg by the infusion of AMPA, but were increased upon inhibition of the RMTg by the infusion of muscimol. By contrast, intra- RMTg infusion of these agents did not change sucrose consumption. Conclusions These data show for the first time that EtOH-drinking and EtOH-seeking behaviors of rats changed inversely with RMTg function, supporting the idea that the RMTg plays a crucial role in EtOH-drinking behaviors. [ABSTRACT FROM AUTHOR]