Nicotine Sensitization in Adult Male and Female Rats Quinpirole-Primed as Neonates

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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 microg/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.