Naloxone and Baclofen attenuate the ethanol’s locomotor activating effects in preweanling Sprague-Dawley rats

ARIAS, C; MLEWSKI, EC; SPEAR, NE; MOLINA, JC

Washington DC

Congreso; Alcoholism Clinical & Experimental Research; 2008

Ethanol exerts biphasic (activating vs sedative) motor activity effects which seem to be associated with different motivational effects (positive vs aversive reinforcement). Heterogenous rats appear to be particularly sensitive to the sedative effects of ethanol, while the activating effects of this drug have been rarely reported in this type of strains. Recently we found that ethanol induces stimulatory effects in preweanling Sprague-Dawley rats during the initial state of the intoxication when employing relatively high ethanol doses (2.5 g/kg). Different animal models suggest that such stimulating effect may be associated by the mesocorticolimbic dopaminergic pathway, and that can be modulated by means of GABA B agonist (Baclofen) or opioid antagonist (Naloxone) treatments. In the present study we analyze if such pharmacological manipulations also reduce the activating effect of ethanol in preweanling Sprague-Dawley pups. Before ethanol administration (0.0 or 2.5 g/kg, intragastrically), 12-day-old pups received different Naloxone (Experiment 1) or Baclofen (Experiment 2) doses. Five minutes after ethanol administration infants were tested in terms of locomotor activity in a novel environment. Naloxone (between 0.5 and 2.0 mg/kg) and low doses of Baclofen (between 1.0 and 2.5 mg/kg or lower) significantly reduced the stimulating effect of ethanol. Higher Baclofen doses (between 5.0 g/kg and 15 mg/kg) did not produce any effect. Neither Baclofen nor Naloxone affected locomotor activity patterns in the corresponding saline-treated controls. During the preweanling period, the opioid and GABA B systems seems to be involved in the stimulating effect of ethanol. These results suggest that early stages in the ontogeny may represent an appropriate experimental framework, alternative to genetic and phylogenetic approaches, for the analysis of mechanisms regulating ethanol-related motor and motivational effects.