Ethanol exposure differentially alters pro-enkephalin mRNA expression in regions of the mesocorticolimbic system

Opioid peptides have been suggested to play a major role in ethanol reinforcement mechanisms and alcohol drinking behaviour. However, in non-selected strains of rodents, it is not known whether opioid biosynthesis is a critical event in these processes.

The aim of this work was to study the effects of a high dose of ethanol (2.5 g/kg body weight) on pro-enkephalin (pro-enk) mRNA expression in brain regions of the mesocorticolimbic system for up to 24 h after drug administration.

Male Wistar rats were administered with ethanol (2.5 g/kg body weight) or distilled water and were killed 30 min, 1, 2, 4, 8 or 24 h after treatment. Coronal brain sections (20 mu) were obtained and pro-enk mRNA expression was studied by in situ hybridization and densitometry.

Acute ethanol administration induced a transient decrease and increase in pro-enk mRNA expression in the ventral tegmental area (33.2%) and prefrontal cortex (26.5%) 2 and 4 h after treatment, respectively. In contrast, ethanol induced prolonged increases in pro-enk mRNA expression in the core and shell regions of the nucleus accumbens, with different kinetics. Maximal effects were observed 2 h after ethanol exposure (core, 70.0%; shell, 60.0%).

Our results indicate that enkephalin expression in regions of the rat mesocorticolimbic system is differentially altered by acute ethanol treatment and suggest that enkephalins may play a key role in ethanol reinforcement mechanisms.