Valproate modulates the expression of methylphenidate (ritalin) sensitization

Abstract

Repeated administration of amphetamine, cocaine, and methylphenidate (MPD) has been reported to elicit behavioral sensitization to their locomotor and stereotypic effects in rodents. GABAergic drugs have been shown to inhibit behavioral effects of stimulants. The objective of the present study was to determine whether single or multiple administration of sodium valproate, a GABA agonist, would prevent the expression of sensitization to the locomotor effect of MPD once it has developed. Twenty-eight male Sprague–Dawley rats were randomized into three treatment groups: a control group received only 2.5 mg/kg MPD during the 14-day cycle, a group received a single 50 mg/kg valproate injection on Day 9, and a group received multiple 50 mg/kg valproate injection on Days 9–13. Rats were housed in test cages and behavioral activities were recorded for 14 consecutive days. All injections were given between 12:00 h and 14:00 h. Multiple injection of MPD elicited sensitization to its locomotor and stereotypic effects. Single administration of valproate did not block the expression of sensitization in the four locomotor indices measured. However, multiple administration of valproate prevented MPD sensitization to horizontal activity, total distance and number of stereotypic movements.