A Test of the Rewarding Versus Aversive Effects of Nicotine in Rats Neonatally Treated with Quinpirole

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Aims: Neonatal quinpirole (a dopamine D2-like agonist) treatment to rats has been shown to increase dopamine D2 receptor sensitivity throughout the animal’s lifetime, and increased dopamine D2 sensitivity is a hallmark of schizophrenia. Schizophrenics are 3 to 4 times more likely to smoke than the normal population, but there is no delineating mechanism. Aim 1: Behaviorally test a rewarding versus averisve dose of nicotine in adolescent rats neonatally treated with quinpirole tested in a place preference paradigm; Aim 2: Analyze phosphorylated cylic AMP response element bidning protein (CREB) in brain areas that mediate drug reward. Methods: Rats were neonatally treated with quinpirole from postnatal days (P)1- 21. After two drug free preferene tests were given in a place preference shuttle box at P41-42, animals were conditioned with saline, a 0.6 or a 1.8 mg/kg free base dose of nicotine for eight consecutive days. A post-conditioning test was given 24 h after conditioning. Time in the paired and unpaired context were measured. Approximately 24 h after the post-condioning test, brain tissue was harvested, flash frozen, and later analyzed for pCREB in the dorsal and nucleus accumbens. Results: Results revealed that neonatal quinpirole enhanced the rewarding associative effects of the lower dose of nicotine compared to animals neonatally treated with saline and conditioned with the same dose of nicotine, which showed a slight place preference. Interestingly, although neonatal saline animals conditioned with the higher dose of nicotine demonstrated conditioned place aversion, neonatal quinpirole treated animals demonstrated no aversion to this same dose. Analyses for p-CREB will be presented. Conclusions: Rats neonatally treated with quinpirole demonstrate an enhancement of the rewarding properties of nicotine, but do not demonstrate an aversion to higher doses of nicotine. These data are congruent with recent self-administration data in our lab, and suggest that increases of dopamine D2 sensitivity may blunt aversive aspects of nicotine.


Phoenix, Arizona

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