Melatonin alters behavior and cAMP levels in nucleus accumbens induced by cocaine treatment.
This study describes the effects of melatonin on cocaine-induced anxiety-like behavior and nucleus accumbens (NAc) cAMP levels in rats. Animals drinking a solution of melatonin (200 ng/ml) at night, either during repeated cocaine administration (15 mg/kg i.p., twice a day for 9 days) or during its withdrawal, showed less anxiety-like behavior in a defensive withdrawal paradigm 48 h after the last injection of cocaine. Melatonin did not alter behavior in control rats treated with saline. Animals exposed for 1 week to unrestricted free-choice oral melatonin self-administration (200 ng/ml) did not show preference for the drinking solution containing melatonin. Pretreatment with melatonin (200 ng/kg i.p. or 200 ng/ml orally) significantly attenuated the augmentation of cAMP levels in NAc following acute cocaine administration (15 mg/kg i.p.). Taken together, these results suggest that a low-dose night-time melatonin treatment results in anxiolytic-like effects in rats withdrawn from repeated cocaine administration, can antagonize cocaine-induced activation of NAc cAMP levels and has low dependence liability.
Zhdanova
Irina V
IV
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. zhdanova@bu.edu
Giorgetti
Marco
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism* / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine; D000242:Cyclic AMP / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism* / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D014151:Anti-Anxiety Agents; D018765:Dopamine Uptake Inhibitors; D000242:Cyclic AMP; D003042:Cocaine; D008550:Melatonin