(-)-Quinpirole hydrochloride

(-)-Quinpirole hydrochloride is an agonist of dopamine D₂-like receptor [1]. 

Dopamine D₂-like receptor reduces neuron’s excitability after activation by dopamine, making it an important drug target in schizophrenia and Parkinson’s disease, but its ligands also cause cognitive inflexibility such as poor reversal learning [1, 2]. 

In spiny neurons, (-)-quinpirole hydrochloride (5 ~ 10 μM) markedly reduced evoked firing in area X and lobus parolfactorius (LPO). Unlike the enhancement of excitability by dopamine D₁ receptor activation, the reduction in evoked firing by (-)-quinpirole hydrochloride was not voltage-dependent. This effect was antagonized by the dopamine D₂-like receptor antagonist sulpiride (10 μM), which suggested that the effect of (-)-quinpirole hydrochloride was specific to dopamine D₂-like receptor [2].

In rats, (-)-quinpirole hydrochloride (0.01, 0.025, 0.1, 0.25, and 0.5 mg/kg) impaired both visual reversal learning task and spatial probabilistic reversal learning (PRL) task in a dose-dependent manner. In analysis of the probe trials on the visual task, (-)-quinpirole hydrochloride at 0.25 mg/kg induced a complete blockade of learning from negative feedback, whilst learning from positive feedback was intact. Estimated parameters from the model that best described the PRL choice data revealed a steep and selective decrease in learning rate from losses [1]. 

References:

[1]. Alsiö J, Phillips B U, Sala-Bayo J, et al. Dopamine D₂-like receptor stimulation blocks negative feedback in visual and spatial reversal learning in the rat: behavioural and computational evidence. Psychopharmacology (Berl), 2019, 236(8): 2307-2323.

[2]. Ding L, Perkel D J. Dopamine modulates excitability of spiny neurons in the avian basal ganglia. The Journal of Neuroscience, 2002, 22(12): 5210-5218.