Brain researchMay 15, 2016

Serotonin7 receptors in the brain's lateral habenula influence depression-like behaviors in rats with Parkinson's symptoms on one side

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Updated Apr 3, 2026

Abstract

Unilateral 6-hydroxydopamine lesions in rats led to depressive-like behaviors as measured by sucrose preference and forced swim tests.

5-HT7 receptors in the lateral habenular nucleus may play a role in regulating depressive-like behaviors associated with Parkinson's disease.
Intra-LHb injection of the 5-HT7 receptor agonist AS19 increased depressive-like behaviors in both sham-operated and lesioned rats.
The 5-HT7 receptor antagonist SB269970 produced antidepressant effects in both groups of rats, but required higher doses in lesioned rats.
AS19 decreased dopamine and serotonin levels in the medial prefrontal cortex, habenula, and hippocampus, while SB269970 increased these levels.
Noradrenaline levels remained unchanged after injections of AS19 or SB269970 in both sham-operated and lesioned rats.

Simplified

Preclinical studies indicate that serotonin7 (5-HT7) receptors may regulate depressive-like behaviors. Depression is a common symptom in Parkinson's disease (PD); however, its pathophysiology is unclear. Here we examined whether 5-HT7 receptors in the lateral habenular nucleus (LHb) involve in the regulation of PD-related depression. Unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta in rats induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. Intra-LHb injection of 5-HT7 receptor agonist AS19 (1, 2 and 4μg/rat) induced or increased the expression of depressive-like behaviors in sham-operated and the lesioned rats. Further, intra-LHb injection of 5-HT7 receptor antagonist SB269970 (1.5, 3 and 6μg/rat) produced antidepressant effects in the two groups of rats. However, the doses producing these effects in the lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-LHb injection of AS19 (4μg/rat) decreased dopamine and 5-HT levels in the medial prefrontal cortex, habenula and hippocampus in sham-operated and the lesioned rats; whereas SB269970 (6μg/rat) increased dopamine and 5-HT levels in these structures. In addition, noradrenaline levels in these structures were not changed after intra-LHb injection of AS19 or SB269970 in the two groups of rats. These findings suggest that activation or blockade of 5-HT7 receptors in the LHb may change the activity of LHb glutamate neurons, and then decreases or increases dopamine and 5-HT levels in the limbic and limbic-related brain regions, which are involved in the regulation of depressive-like behaviors.

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Serotonin7 receptors in the brain's lateral habenula influence depression-like behaviors in rats with Parkinson's symptoms on one side

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