Abstract
Rationale
Increases in dopamine D2-like receptor function are common in several psychological disorders that demonstrate a four to five fold increase in nicotine abuse compared to the general population.
Objective
The objective of this study was to analyze the interaction of sex differences and sensitization to nicotine in rats D2 receptor primed as neonates.
Materials and methods
A total of 32 male and 32 female Sprague-Dawley rats derived from eight litters were ontogenetically treated with quinpirole (1 mg/kg) or saline from postnatal days (P) 1–21 and raised to adulthood. At P60, all animals were given an acute injection of quinpirole HCl (100 μg/kg) and yawns were counted for 1 h. Yawning has been shown to be a behavioral event mediated by D2-like receptors. Beginning on P61–65, animals were habituated to a locomotor arena and subsequently administered either nicotine (0.5 mg/kg free base) or saline (intraperitoneal) every second day for 3 weeks. Approximately 15 min after each injection, animals were placed into the arena and horizontal activity and vertical rears were recorded.
Results
A robust increase of yawning was observed at P60 in D2 primed as compared to saline controls. Priming of D2-like receptors increased the locomotor response to nicotine in horizontal activity in both males and females, but females demonstrated a more robust hypoactive locomotor response to initial nicotine treatment when compared to saline-treated females. Nicotine also produced a significant decrease of vertical rearing in both males and females.
Conclusions
It appears that D2 receptor priming enhances sensitization to nicotine in adult rats, and females may be more behaviorally sensitive to nicotine than males.
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Perna, M.K., Cope, Z.A., Maple, A.M. et al. Nicotine sensitization in adult male and female rats quinpirole-primed as neonates. Psychopharmacology 199, 67–75 (2008). https://doi.org/10.1007/s00213-008-1128-5
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DOI: https://doi.org/10.1007/s00213-008-1128-5