Infralimbic D2 receptors are necessary for fear extinction and extinction-related tone responses.
Submitted by Gregory Quirk on
Title | Infralimbic D2 receptors are necessary for fear extinction and extinction-related tone responses. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Mueller, D, Bravo-Rivera, C, Quirk, GJ |
Journal | Biol Psychiatry |
Volume | 68 |
Issue | 11 |
Pagination | 1055-60 |
Date Published | 2010 Dec 1 |
ISSN | 1873-2402 |
Keywords | Action Potentials, Animals, Conditioning (Psychology), Dopamine Antagonists, Extinction, Psychological, Fear, Limbic System, Male, Motor Activity, Neurons, Prefrontal Cortex, Raclopride, Rats, Rats, Sprague-Dawley, Receptors, Dopamine D2 |
Abstract | BACKGROUND: Fear extinction is dependent on plasticity in the infralimbic prefrontal cortex, an area heavily innervated by midbrain dopaminergic inputs. Dopamine D2 receptors are concentrated in infralimbic output neurons that are involved in the suppression of conditioned fear after extinction. Here, we examined the specific role of infralimbic D2 receptors in mediating associative learning underlying fear extinction using the selective D2 antagonist raclopride. METHODS: Raclopride was administered systemically or infused into the infralimbic prefrontal cortex before fear extinction, and extinction retention was tested the following day. Rats were also prepared for single-unit recording in the infralimbic prefrontal cortex to assess the effect of raclopride on firing properties. RESULTS: We found that systemic injection of raclopride given before extinction impaired retrieval of extinction when rats were tested drug-free the next day but also induced catalepsy during extinction training. To determine whether impaired extinction was due to impaired motor function or disruption of extinction consolidation, we infused raclopride directly into the infralimbic prefrontal cortex. Raclopride infused immediately before extinction training did not produce motor deficits but impaired recall of extinction when tested drug-free. Furthermore, in animals that underwent extinction training, systemic raclopride reduced the tone responsiveness of infralimbic prefrontal cortex neurons in layers 5/6, with no changes in average firing rate. CONCLUSIONS: We suggest that D2 receptors facilitate extinction by increasing the signal-to-noise of infralimbic prefrontal cortex neurons that consolidate extinction. |
DOI | 10.1016/j.biopsych.2010.08.014 |
Alternate Journal | Biol. Psychiatry |
PubMed ID | 20926066 |
PubMed Central ID | PMC2981677 |
Grant List | MH058883 / MH / NIMH NIH HHS / United States MH081975 / MH / NIMH NIH HHS / United States R01 MH058883 / MH / NIMH NIH HHS / United States R01 MH058883-11 / MH / NIMH NIH HHS / United States R01 MH081975 / MH / NIMH NIH HHS / United States R01 MH081975-01A1 / MH / NIMH NIH HHS / United States |