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

Sci Rep. 2022 Aug 19;12(1):14131. doi: 10.1038/s41598-022-18081-3.

Abstract

Dopamine has been implicated in the reinforcing effects of smoking. However, 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 differences in the effects of dopaminergic drugs on behavior. 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 after treatment. Operant responding for nicotine and food and locomotor activity were decreased immediately after treatment with SCH 23390. Treatment with SCH 23390 did not have any long-term effects. Operant responding for nicotine was still decreased 48 h after treatment with A77636, and food responding was decreased up to 24 h after treatment. Treatment with A77636 only decreased locomotor activity at the 48 h time point. There were no sex differences in the effects of SCH 23390 or A77636. In conclusion, 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 does not cause sedation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzazepines
  • Conditioning, Operant
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dopamine* / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Nicotine* / pharmacology
  • Rats
  • Receptors, Dopamine D1 / agonists
  • Smoking

Substances

  • Benzazepines
  • Dopamine Agonists
  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • Nicotine
  • Dopamine