Neonatal administration of monosodium glutamate prevents the development of ethanol- but not psychostimulant-induced sensitization: a putative role of the arcuate nucleus.

Lesions of the arcuate nucleus by monosodium glutamate, goldthioglucose and oestradiol valerate treatments are known to prevent the acute stimulating effect of ethanol in mice. On the basis of these results, the current study analysed whether a lesion of the arcuate nucleus by monosodium glutamate was able to block ethanol-induced locomotor sensitization. To produce the arcuate nucleus lesions, pups were injected with saline or monosodium glutamate (4 mg/g body weight) subcutaneously on 5 alternate days, starting on postnatal day one. Sensitization treatments began 10 weeks after the initial lesions. Sensitization training consisted of six trials on alternate days, in which groups of mice were treated with ethanol (2 g/kg) or saline, and then tested in an open-field for the induction of locomotor activity. The present study demonstrated that animals with monosodium glutamate-induced lesions did not develop locomotor sensitization to ethanol. Different groups of mice were used to assay blood ethanol levels and to evaluate the effect of arcuate nucleus lesions on psychostimulant-induced locomotor sensitization. Sensitization to cocaine or amphetamine was spared in monosodium glutamate-pre-treated animals, although the lesion of arcuate nucleus reduced the sensitivity of mice to cocaine. Our findings therefore suggest that the arcuate nucleus may be critical for the neuroadaptations that underlie the behavioural sensitization to ethanol, in contrast to those mediating psychostimulant-induced sensitization.