Preadolescent dopamine receptor antagonism increases postadolescent reward-related operant behaviors that may depend on dopamine receptor hypersensitivity.

Abstract:

: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.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Holahan MR,Goheen K

doi

10.1016/j.neulet.2020.134917

subject

Has Abstract

pub_date

2020-04-23 00:00:00

pages

134917

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(20)30187-7

journal_volume

725

pub_type

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