The dopaminergic system has a long history of being associated with reward-related activities but the developmental consequences of blocking dopamine receptor function on reward-based associative learning has been less studied. To this end, male, Long Evans rats were systemically (i.p.) treated with the dopamine receptor (DAr) antagonist, flupenthixol (0.25 mg/kg), or saline, from postnatal day (P)18 – 24 (preadolescence) then trained on an operant conditioning task from P41 – P45 (postadolescent) without drug treatment. The preadolescent flupenthixol group showed elevated active lever responses and locomotor activity during the drug-free test. Another group of rats was given flupenthixol prior to each acquisition session from P41 – 45 which significantly suppressed both active lever presses and locomotor activity. Separate groups of rats were treated with flupenthixol or saline from P18 – 24 then treated with apomorphine or saline on P41 followed by assessment of c-Fos labeling in the nucleus accumbens. Early flupenthixol treatment was associated with more apomorphine-induced c-Fos labeling in the nucleus accumbens shell than the early saline-apomorphine group, indicating a sensitized response. These findings suggest that preadolescent dopamine receptor blockade may lead to a sensitized postadolescent dopaminergic response that underlies enhanced behavioral responses in the presence of rewarding stimuli.
Copyright © 2020. Published by Elsevier B.V.