Dopamine D1-like receptor blockade and stimulation decreases operant responding for nicotine and food in male and female rats

Abstract

Dopamine has been implicated in smoking, but there remains a need for a better understanding of the effects of dopamine D1-like receptor agonists on nicotine intake and the role of sex in the effects of dopaminergic drugs on nicotine intake. This work studied the effects of D1-like receptor stimulation and blockade on operant responding for nicotine and food and locomotor activity in male and female rats. The effects of the D1-like receptor antagonist SCH 23390 (0.003, 0.01, 0.03 mg/kg) and the D1-like receptor agonist A77636 (0.1, 0.3, 1 mg/kg) on responding for nicotine and food, and locomotor activity were investigated. The effects of SCH 23390 were investigated 15 min and 24 h after treatment, and the effects of the long-acting drug A77636 were investigated 15 min, 24 h, and 48 h later. Operant responding for nicotine and food was decreased 15 min, but not 24 h, after treatment with SCH 23390. Operant responding for nicotine was decreased 15 min, 24 h, and 48 h after treatment with A77636, and food responding was decreased 15 min and 24 h later. Locomotor activity was decreased 15 min, but not 24 h, after treatment with SCH 23390. A77636 only decreased locomotor activity 48 h after treatment. There were no sex differences in the effects of SCH 23390 or A77636. In conclusions, the D1-like receptor antagonist SCH 23390 reduces nicotine intake and causes sedation in rats. Stimulation of D1-like receptors with A77636 decreases nicotine intake at time points that the drug is not sedative.

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

“…In this study, we did not find a sex difference in operant responding for food pellets. This is in line with previous studies that reported that there are no sex differences in operant responding for food pellets in rats (Chellian et al, 2020c;Chellian et al, 2022).…”

“…On a similar note, treatment with flupentixol induced a greater decrease in food intake than L-741626. This work is in line with studies that showed that blockade of D1-like receptors induces a relatively large decrease in nicotine and food intake in rats (Chellian et al, 2022; Corrigall and Coen, 1991). In contrast, treatment with the D2-like receptor antagonist spiperone (and also serotonin 5-HT1A and serotonin 5-HT2A antagonist) induces a relatively small decrease in nicotine and food intake in rats (Corrigall and Coen, 1991; Metwally et al, 1998).…”

“…Our laboratory has conducted numerous nicotine self-administration studies in rats of both sexes. In a recent study with a similar design (food training followed by IV nicotine intake) and nicotine dose (0.06 mg/kg/inf), we did not observe a sex difference in nicotine intake (Chellian et al, 2022). In other studies, in which the rats were trained to respond for food pellets before the self-administration of a lower dose of nicotine, 0.03 mg/kg/inf, we also did not observe a sex difference in nicotine intake (Chellian et al, 2020a;Chellian et al, 2021b).…”

“…In the second experiment, the females displayed more rearing than the males, but there was no sex difference in locomotor activity (i.e., distance traveled). Our previous studies showed that females display more locomotor activity and rearing in open field tests (Chellian et al, 2022;Knight et al, 2021). Sex differences in open field behavior and other behavioral tests are relatively small, and because of the relatively small groups sizes in animal studies, many studies do not have the statistical power to conclude that there are sex differences.…”

Mifepristone decreases nicotine intake in dependent and non-dependent adult rats

“…The catheters were implanted as described before [32][33][34]. The rats were anesthetized with an isoflurane-oxygen vapor mixture (1-3%) and prepared with a catheter in the right jugular vein.…”