Neurotensin in the nucleus accumbens reverses dopamine supersensitivity evoked by antipsychotic treatment

Neuropharmacology
Alice ServonnetAnne-Noël Samaha

Abstract

Long-term exposure to antipsychotics like haloperidol can increase sensitivity to dopamine agonist stimulation. This could contribute to treatment failure and increase relapse to psychosis. Chronic antipsychotic treatment elevates neurotensin levels in the nucleus accumbens (NAc), where the neuropeptide modulates dopamine function by signalling through NTS1 receptors. We hypothesized that increasing neurotensin activity in the NAc attenuates the expression of antipsychotic-induced dopamine supersensitivity, which is indicated by a potentiated psychomotor response to amphetamine. Rats received either continuous (CONT-HAL; achieved via subcutaneous osmotic minipump) or intermittent (INT-HAL; achieved via daily subcutaneous injection) haloperidol treatment for 16-17 days. Three to 5 days later, we injected neurotensin into the NAc and measured amphetamine-induced locomotion. Only CONT-HAL rats showed potentiated amphetamine-induced locomotion, indicating dopamine supersensitivity. Compared to intra-NAc saline, intra-NAc neurotensin suppressed amphetamine-induced locomotion in CONT-HAL rats, but not in INT-HAL or control rats. In a new cohort of CONT-HAL and INT-HAL rats, we measured striatal levels of proneurotensin mRNA and NTS1 ...Continue Reading

Citations

Feb 13, 2020·Current Opinion in Psychiatry·Ilse A ThompsonIris E C Sommer
Dec 22, 2020·Behavioural Brain Research·Alice ServonnetAnne-Noël Samaha
Dec 4, 2019·Neuroscience and Biobehavioral Reviews·Benjamín RodríguezMirian A F Hayashi
Feb 15, 2020·Neuropharmacology·María Luisa Torruella-Suárez, Zoe A McElligott
Feb 19, 2021·Endocrinology·Jariel Ramirez-Virella, Gina M Leinninger

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