NeuropharmacologyJul 11, 2021

Blocking GABAB receptors before or after nerve signals in the lateral habenula affects anxiety-like behavior differently in a rat model of Parkinson’s disease

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 3, 2026

Abstract

Unilateral 6-hydroxydopamine lesions in rats reduced extracellular dopamine levels in the basolateral amygdala and induced anxiety-like behaviors.

Lesioned rats exhibited hyperactivity of lateral habenula neurons compared to sham-lesioned rats.
Injection of a pre-synaptic GABA receptor antagonist produced anxiolytic-like effects, while a post-synaptic antagonist induced anxiety-like responses.
The pre-synaptic antagonist decreased neuron firing rates and increased the GABA/glutamate ratio in the lateral habenula.
The doses needed for behavioral effects in lesioned rats were lower than those in sham-lesioned rats.
Degeneration of the nigrostriatal pathway may enhance the function or expression of GABA receptors in the lateral habenula.

Simplified

Although the output of the lateral habenula (LHb) controls the activity of midbrain dopaminergic and serotonergic systems, which are implicated in the pathophysiology of anxiety, it is not known how blockade of GABAreceptors in the region affects anxiety-like behaviors, particularly in Parkinson's disease-related anxiety. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, led to hyperactivity of LHb neurons and decreased the level of extracellular dopamine (DA) in the basolateral amygdala (BLA) compared to sham-lesioned rats. Intra-LHb injection of pre-synaptic GABAreceptor antagonist CGP36216 produced anxiolytic-like effects, while the injection of post-synaptic GABAreceptor antagonist CGP35348 induced anxiety-like responses in both groups. Further, intra-LHb injection of CGP36216 decreased the firing rate of the neurons, and increased the GABA/glutamate ratio in the LHb and release of DA and serotonin (5-HT) in the BLA; conversely, CGP35348 increased the firing rate of the neurons and decreased the GABA/glutamate ratio and release of DA and 5-HT in sham-lesioned and the lesioned rats. However, the doses of the antagonists producing these behavioral effects in the lesioned rats were lower than those in sham-lesioned rats, and the duration of action of the antagonists on the firing rate of the neurons and release of the neurotransmitters was prolonged in the lesioned rats. Collectively, these findings suggest that pre-synaptic and post-synaptic GABAreceptors in the LHb are involved in the regulation of anxiety-like behaviors, and degeneration of the nigrostriatal pathway up-regulates function and/or expression of these receptors. B B B B

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Blocking GABAB receptors before or after nerve signals in the lateral habenula affects anxiety-like behavior differently in a rat model of Parkinson’s disease

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