Diverging changes in rat striatal extracellular dopamine and DOPAC levels and in frequency-modulated 50-kHz ultrasonic vocalizations rate during repeated amphetamine treatment

One characteristic feature of addictive drugs is their ability to induce, after a single exposure, a lasting sensitization to the next doses; the underlying neuroplastic changes supposedly involve the brain dopamine system. We aimed at identifying putative relationships between alterations in extracellular dorsal striatal dopamine, HVA and DOPAC levels and in frequency-modulated 50-kHz ultrasonic vocalizations rate response during repeated intraperitoneal amphetamine treatment. Measurements were performed before and after amphetamine doses 1, 2, 7 and 8 (Amph1, Amph2, Amph7 and Amph8; treatment days 1, 7, 12 and 23, respectively). Amphetamine was confirmed to induce sensitization of the vocalization response, but an extended recording time (180 instead of 20 min) revealed that sensitization of this response requires more time to develop than hitherto believed. Baseline extracellular dopamine level increased initially, declined after a series of daily amphetamine doses and showed some tendency for recovery after drug withdrawal. Baseline extracellular DOPAC (but not HVA) showed a continuous decline during the treatment. There was no significant change in the integrated short-term (3-h) extracellular dopamine response, whereas the respective DOPAC collection lowered significantly after repeated drug treatment. Extracellular DOPAC is believed to originate mostly from newly synthesized dopamine, hence the declines in its baseline and post-amphetamine levels suggest falling dopamine synthesis. These results indicate that sensitization of the appetitive vocalization response to amphetamine continues despite reduced dorsal striatal dopamine synthesis and involves no changes in amphetamine-induced dopamine release.