AbstractThe 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.

2020-12-01·Journal of Psychopharmacology3区 · 医学

Selective activation of D1 dopamine receptors exerts antidepressant-like activity in rats

3区 · 医学

Article

作者: Demars, Fanny ; Lavergne, Francis ; Desormeaux, Cleo ; Jay, Therese M ; Davenas, Elisabeth

Background: Major depressive disorder is a common illness that severely decreases psychosocial functioning. Due to the major limitations of current treatments including response failure, it is crucial to develop better therapy strategies. Evidence suggests that dopamine dysregulation might play a major role in major depressive disorder physiopathology. Aims: This study investigates whether the dopamine D1 receptor agonist A77636 modulates antidepressant-like activity in rats. Methods: Rats were injected with an acute single dose of A77636 (0.75, 1.5 or 3 mg/kg), a potent and selective dopamine D1-like receptor agonist. Their locomotor activity, social interactions and behavioural response to the forced swim test were analysed 30 min after the injection. Results: During the forced swim test, the D1 agonist dose dependently reduced the immobility while the time of bursting was increased. Social interactions were significantly increased in the animals exposed to 3 mg/kg of A77636 whereas no significant changes were measured in general motor activity. Conclusions: The present results provide evidence that pharmacological modulation of D1 receptor by the selective agonist A77636 induces antidepressant-like effects in rats, which encourages further studies regarding D1-specific modulation in major depressive disorder treatment.

2015-06-01·Neuroscience3区 · 医学

D1 receptors in the nucleus accumbens-shell, but not the core, are involved in mediating ethanol-seeking behavior of alcohol-preferring (P) rats

3区 · 医学

Article

作者: Knight, C P ; Hauser, S R ; McBride, W J ; Rodd, Z A ; Dhaher, R ; Deehan, G A ; Wilden, J A

Clinical and preclinical research suggest that activation of the mesolimbic dopamine (DA) system is involved in mediating the rewarding actions of drugs of abuse, as well as promoting drug-seeking behavior. Inhibition of DA D1 receptors in the nucleus accumbens (Acb) can reduce ethanol (EtOH)-seeking behavior of non-selective rats triggered by environmental context. However, to date, there has been no research on the effects of D1 receptor agents on EtOH- seeking behavior of high alcohol-preferring (P) rats following prolonged abstinence. The objective of the present study was to examine the effects of microinjecting the D1 antagonist SCH 23390 or the D1 agonist A-77636 into the Acb shell or Acb core on spontaneous recovery of EtOH-seeking behavior. After 10 weeks of concurrent access to EtOH and water, P rats underwent seven extinction sessions (EtOH and water withheld), followed by 2 weeks in their home cages without access to EtOH or operant sessions. In the 2nd week of the home cage phase, rats were bilaterally implanted with guide cannula aimed at the Acb shell or Acb core; rats were allowed 7d ays to recover before EtOH-seeking was assessed by the Pavlovian Spontaneous Recovery (PSR) model. Administration of SCH23390 (1μg/side) into the Acb shell inhibited responding on the EtOH lever, whereas administration of A-77636 (0.125μg/side) increased responding on the EtOH lever. Microinfusion of D1 receptor agents into the Acb core did not alter responding on the EtOH lever. Responses on the water lever were not altered by any of the treatments. The results suggest that activation of D1 receptors within the Acb shell, but not Acb core, are involved in mediating PSR of EtOH-seeking behavior of P rats.

100 项与 A-77636 相关的药物交易

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