The D1/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 decrease operant responding for nicotine and food and locomotor activity in male and female rats.

Ranjithkumar Chellian, Azin Behnood-Rod, Ryann Wilson, Karen Lin, Grace Wing-Yan King, Adriaan W Bruijnzeel

Journal of psychopharmacology (Oxford, England) 2023 Feb

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The reinforcing properties of nicotine play a critical role in smoking and vaping. There is a need for treatments that decrease the reinforcing properties of nicotine and thereby improve smoking and vaping rates. Dopamine plays a role in the reinforcing properties of nicotine, but little is known about the role of dopamine D2-like receptors in nicotine intake and whether there are sex differences in the effects of dopaminergic drugs on nicotine intake. The goal of the present studies was to investigate the effects of the D1/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 on nicotine self-administration in male and female rats. The effects of flupentixol and L-741626 on operant responding for nicotine and food and locomotor activity in a small open field were investigated. There were no sex differences in baseline nicotine intake. The D1/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 decreased operant responding for nicotine. Blockade of D1/D2-like receptors and blockade of D2-like receptors also decreased operant responding for food and decreased locomotor activity. Flupentixol induced a greater decrease in operant responding for food in males than females. However, in the other tests, there were no sex differences in the effects of the dopamine receptor antagonists. Blockade of D1/D2-like receptors with flupentixol and D2-like receptors with L-741626 decreases nicotine and food intake in rats of both sexes. These compounds also decrease locomotor activity which might be indicative of a sedative effect.

Citation

Ranjithkumar Chellian, Azin Behnood-Rod, Ryann Wilson, Karen Lin, Grace Wing-Yan King, Adriaan W Bruijnzeel. The D1/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 decrease operant responding for nicotine and food and locomotor activity in male and female rats. Journal of psychopharmacology (Oxford, England). 2023 Feb;37(2):216-228