Moxonidine, a selective imidazoline-1 receptor agonist, suppresses the effects of ethanol withdrawal on the acoustic startle response in rats

Background: There is a need for improved treatments for ethanol withdrawal in humans. Previously, ethanol withdrawal has been shown to enhance the acoustic startle response in rats. Because many ethanol withdrawal symptoms are caused by autonomic hyperactivity, we examined the effects of two antihypertensives, the imidazoline(I)1 agonist moxonidine and the α2-adrenergic partial agonist clonidine, on the ethanol-withdrawal-enhanced acoustic startle response in rats. d-amphetamine-enhanced startle served as a positive control. Methods: Male, Long-Evans rats were made ethanol-dependent through unlimited access to liquid diet containing 6.7% v/v ethanol for 10 days. The concentration of ethanol was reduced to 3.3% v/v on the 11th day. On the 12th day, the rats received control diet. The acoustic startle response was tested 24 hours following the withdrawal of ethanol. Control rats were maintained on control liquid diet throughout the experiment. Results: As has been shown previously, withdrawal from the chronic ingestion of ethanol significantly enhanced the acoustic startle response. Pretreatment with moxonidine (0.01, 0.1, and 1.0 mg/kg, subcutaneously), but not clonidine (0.3, 1.0, and 3.0 mg/kg, subcutaneously), significantly attenuated the ethanol withdrawal-induced elevation of the acoustic startle response. Moxonidine did not suppress the elevation in the startle response caused by d-amphetamine. Conclusions: These results indicate that I1 receptors can play an important role in ethanol withdrawal and that moxonidine may be useful for the treatment of ethanol withdrawal in humans.