| Abstract No.: | B-C2097 |
| Country: | Canada |
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| Title: | REPEATED AMPHETAMINE EXPOSURE DISRUPT DOPAMINERGIC REGULATION OF THE BASOLATERAL AMYGDALA-PREFRONTAL CORTICAL PATHWAY |
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| Authors/Affiliations: | 1 Maric Tse*; 1 Stan Floresco;
1 University of British Columbia, Vancouver, BC, Canada
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| Content: | Projections from basolateral amygdala (BLA) to the prefrontal cortex (PFC) form a neural circuit that regulates certain emotional and cognitive processes, and recent studies indicate that abuse of psychostimulants such as amphetamine (AMPH) is associated with impairments in the emotional and decision-making responses regulated by the BLA-PFC circuits. Previous work has shown that mesocortical dopamine (DA) input from the ventral tegmental area (VTA exerts a powerful neuromodulatory influence over inhibitory and excitatory transmission in this pathway. The present study assessed the effects of repeated AMPH exposure on dopaminergic regulation of changes in PFC neural activity driven by inputs from the BLA, using single-unit recordings in urethane-anesthetized Sprague-Dawley rats. Animals initially received 5 injections of either saline or d-AMPH (2mg/kg every 2 days for 10 days). After a 2-4 week drug washout period, rats were anesthetized and implanted with extracelluar recording electrodes in the medial PFC and stimulating electrodes in the BLA and VTA. The majority of PFC neurons displayed a robust inhibition of spontaneous firing in response to BLA stimulation. However, in AMPH-treated rats, higher stimulation current intensities were required to induce the same duration of inhibition observed in controls, suggested a decrease in GABAergic activity. In saline-treated rats, burst stimulation of the VTA caused 1) an increase (~100%) in the spontaneous firing rate of PFC neurons during VTA stimulation and 2) a reduction (~50%) in the duration of BLA-evoked inhibition of PFC neural activity that persisted 2-10 min after VTA stimulation, as we have reported previously. In stark contrast, VTA stimulation neither increased the firing rate of PFC neurons, nor did it reduce the duration of BLA-evoked inhibition in AMPH-treated rats. In a separate population of neurons, BLA stimulation evoked a monosynaptic excitatory response. In saline-treated rats, burst stimulation of the VTA prior to BLA stimulation caused a near complete suppression of BLA-evoked firing; this effect was less pronounced in AMPH-treated animals. These data indicate that repeated AMPH exposure disrupts the neuromodulatory control that VTA DA inputs exert over changes in PFC neural activity driven by the BLA. These neurophysiological alterations that are induced by repeated AMPH exposure may be an underlying cause of the maladaptive cognitive, emotional and behavioral processes exhibited by chronic psychostimulant abusers. |
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