Expression of sensitization to amphetamine and dynamics of dopamine neurotransmission in different laminae of the rat medial prefrontal cortex

The present study investigated the effect of acute and repeated administrat ions of amphetamine (AMPH) on dopamine (DA), 3,4-dihydroxyphenyiacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the two main cytoarchitectonic subterritories of the medial prefrontal c ortex (mPFC) (anterior cingulate and dorsocaudal prelimbic cortices vs vent ral prelimbic and rostral infralimbic cortices). Both the acute locomotor e ffects of AMPH and the expression of behavioral sensitization following its repeated administration were also simultaneously assessed. The repeated, i ntermittent administration of AMPH over five consecutive days led to a sign ificant sensitized locomotor response to a subsequent challenge that occurr ed following a 48-h withdrawal period. Basal dialysate DA levels were highe r in the ventral mPFC compared with its dorsal counterpart in naive animals , that is prior to the acute administration of AMPH. However, the inverse r elationship was observed in animals that had developed sensitization: basal dialysate DA levels were significantly lower in the ventral mPFC compared with the dorsal mPFC. In naive animals, AMPH produced a significant decreas e in DA levels in both the ventral and dorsal subregions of the mPFC. Howev er, the inverse relationship was observed in animals that had developed sen sitization: dialysate DA levels in response to AMPH remained significantly decreased in the dorsal mPFC, whereas DA went back to baseline levels in th e ventral mPFC. Given that a critical concentration of DA is required for n ormal function of the mPFC, our results suggest that AMPH-induced changes i n DA levels in different subregions of the mPFC are critical for both the a cute effects of the drug and the expression of behavioral sensitization to its repeated administration by producing either less or more selectivity or sharpening of stimuli to corticocortical dendrites and subcortical synapti c afferents to the pyramidal cells located in the dorso-ventral axis of the mPFC. (C) 2001 Elsevier Science Ltd. All rights reserved.