Dopamine D1-like receptor activation decreases nicotine intake in rats with short or long access to nicotine

Addict Biol. 2023 Aug;28(8):e13312. doi: 10.1111/adb.13312.


The use of nicotine and tobacco products is highly addictive. The dopaminergic system plays a key role in the initiation and maintenance of nicotine intake. Dopamine D1-like receptor blockade diminishes nicotine intake in rats with daily short (1 h) access to nicotine, but little is known about the effects of dopamine receptor antagonists or agonists on nicotine intake in rats with intermittent long (23 h) access. Because of the extended access conditions and high nicotine intake, the intermittent long access procedure might model smoking and vaping better than short access models. We investigated the effects of the dopamine D1-like receptor antagonist SCH 23390 and the D1-like receptor agonist A77636 on nicotine intake in male rats with intermittent short or long access to nicotine. The rats self-administered nicotine for 5 days (1 h/day) and were then given 15 intermittent short (1 h/day) or long (23 h/day) access sessions (3 sessions/week, 0.06 mg/kg/inf). The D1-like receptor antagonist SCH 23390 decreased nicotine intake to a similar degree in rats with short or long access to nicotine. The D1-like receptor agonist A77636 induced a greater decrease in nicotine intake in the rats with long access to nicotine than in rats with short access. Treatment with A77636 induced a prolonged decrease in nicotine intake that lasted throughout the dark and light phase in the long access rats. These findings indicate that blockade and stimulation of D1-like receptors decrease nicotine intake in an intermittent long access animal model that closely models human smoking and vaping.

Keywords: D1-like receptors; dopamine; long access; nicotine; rats; self-administration; short access.

Publication types

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

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Benzopyrans
  • Dopamine*
  • Humans
  • Male
  • Nicotine* / pharmacology
  • Rats
  • Receptors, Dopamine D1


  • Nicotine
  • A 77636
  • Dopamine
  • Receptors, Dopamine D1
  • Benzopyrans
  • Benzazepines