AMPHETAMINE ADMINISTERED TO THE VENTRAL TEGMENTAL AREA SENSITIZES RATS TO THE LOCOMOTOR EFFECTS OF NUCLEUS-ACCUMBENS AMPHETAMINE

This experiment investigated whether pre-exposure to injections of amp hetamine into the ventral tegmental area (VTA) sensitizes the locomoto r response to a subsequent test injection of amphetamine given into th e nucleus accumbens (N.Acc.). Different groups of rats received three intra-VTA injections of amphetamine (2.5 mu g/0.5 mu l/side) or saline (0.5 mu l/side), one injection given every 3rd day, and locomotor act ivity was measured for 60 min. Seven to 10 days later, all animals wer e tested with an intra-N.Acc. challenge injection of amphetamine (0, 1 .5, 2.5 or 5.0 mu g/0.5 mu l/side) and locomotor activity was again me asured. In agreement with previous reports, intra-VTA amphetamine prod uced no behavioral effects acutely. However, when animals were subsequ ently challenged with an injection of amphetamine into the N.Acc., ani mals pre-exposed to intra-VTA amphetamine showed significantly and dos e-dependently greater levels of locomotor activity than saline pre-exp osed rats. Animals preexposed to amphetamine in sites outside the VTA did not show sensitized responding when subsequently tested with intra -N.Acc. amphetamine. These findings support the view that the inductio n of behavioral sensitization to amphetamine results from an action of this drug in the cell body region of mesolimbic dopamine neurons (VTA ), whereas its expression reflects an enhanced reactivity in the termi nals of these neurons in the N.Acc. Implications of such findings for the molecular neurobiological basis of behavioral sensitization to amp hetamine are discussed.