J. Vandergriff et al., Moxonidine, a selective imidazoline-1 receptor agonist, suppresses the effects of ethanol withdrawal on the acoustic startle response in rats, BIOL PSYCHI, 47(10), 2000, pp. 874-879
Background: There is a need for improved treatments for ethanol withdrawal
in humans. Previously, ethanol withdrawal has been shown to enhance the aco
ustic startle response in rats. Because many ethanol withdrawal symptoms ar
e caused by autonomic hyperactivity, we examined the effects of two antihyp
ertensives, the imidazoline(I)(1) agonist moxonidine and the alpha(2)-adren
ergic partial agonist clonidine, on the ethanol-withdrawal-enhanced acousti
c startle response in rats. d-amphetamine-enhanced startle sewed as a posit
ive control.
Methods: Male, Long-Evans rats were made ethanol-dependent through unlimite
d access to liquid diet containing 6.7% v/v ethanol for 10 days. The concen
tration 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 ingestio
n of ethanol significantly enhanced the acoustic startle response. Pretreat
ment with moxonidine (0.01, 0.1, and 1.0 mg/kg, subcutaneously), but not cl
onidine (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 b
y d-amphetamine.
Conclusions: These results indicate that I, receptors can play an important
role in ethanol withdrawal and that moxonidine may be useful for the treat
ment of ethanol withdrawal in humans. (C) 2000 Society of Biological Psychi
atry.