Mianserin, but not Ondansetron, reduces the locomotor stimulating effect of ethanol in preweanling rats

During infancy rats are highly sensitive to the locomotor stimulating effect of ethanol, an effect particularly observed when they are tested during the rising phase of the blood ethanol curve and in a novel environment. According to a recent study infant rats require some degree of stress to get stimulated after being challenged with ethanol. Ethanol-induced stimulation in preweanling rats required the activation of CRH-1 receptors. Considering these antecedents, we explored modulation of the acute stimulating effect of ethanol (2.5 g/kg) by two anxiolytic drugs, Mianserin (2.5 or 5 mg/kg) and Ondansetron (1 or 3 mg/kg). Mianserin attenuated the stimulating effect of ethanol at a dose that did not affect locomotor activity in water-controls, likely acting through 5-HT2 receptors, while Ondansetron, a 5-HT3 antagonist, did not affect this response. These results are consistent with recent findings indicating that one of the mechanisms by which the CRH-1 receptor modulates anxiety depends on sensitization of the 5-HT2 receptor antagonist, and highlight the importance of stress as a modulator of the effects of ethanol during early developmental stages. (C) 2011 Elsevier Inc. All rights reserved.