Effects of an adenosine A agonist on the rewarding associative properties of nicotine and neural plasticity in a rodent model of schizophrenia.

BACKGROUND

Adenosine A receptors form a mutually inhibitory heteromeric complex with dopamine D receptors such that each receptor exhibits lower sensitivity to its agonist after the opposing receptor agonist is bound. This study analyzed the effects of CGS 21680, an adenosine A agonist, on nicotine conditioned place preference (CPP) in adolescence using a rodent model of schizophrenia (SZ).

METHODS

Rats were treated from postnatal day (P) 1 to P21 with saline or the dopamine D/D agonist quinpirole (NQ treatment) and raised to P41. After an initial preference test, rats were conditioned with saline or nicotine (0.6 mg/kg base) from P43 to P51. CGS 21680 (0.03 or 0.09 mg/kg) was given 15 minutes before nicotine was administered. The post-conditioning test was administered on P52. On P53, the nucleus accumbens (NAcc) was analyzed for brain-derived neurotrophic factor (BDNF) and glial cell-lined neurotrophic factor (GDNF).

RESULTS

Results revealed that NQ treatment enhanced nicotine CPP, and both doses of CGS 21680 alleviated this enhancement. Nicotine also resulted in a CPP in controls, which was alleviated by both doses of CGS 21680. BDNF closely followed the behavioral results: CGS 21680 alleviated the enhancement in NAcc BDNF in NQ-treated animals, and eliminated the increase in NAcc BDNF produced by nicotine in controls. NQ-treated animals conditioned to nicotine resulted in an increase of NAcc GDNF, but this was eliminated by CGS 21680. Both BDNF and GDNF correlated with CPP performance.

CONCLUSIONS

Results revealed that an adenosine A agonist decreased the rewarding aspects of nicotine and its accompanying neural plasticity changes in a model of SZ.