Diverse behavioral, monoaminergic and Fos protein responses to opioids in Warsaw high-alcohol preferring and Warsaw low-alcohol preferring rats

作者：Taracha Ewa^*; Dyr Wanda; Cwiek Marta; Turzynska Danuta; Walkowiak Jerzy; Wyszogrodzka Edyta; Kostowski Wojciech; Plaznik Adam; Chrapusta Stanislaw J

来源：Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2011, 35(2): 588-597.

DOI：10.1016/j.pnpbp.2010.12.028

• Alcohol preference
• Behavioral sensitization
• Fos protein
• Methadone
• Monoamines
• Morphine

Predisposition to addictions is presumably related to a dysfunction of the brain reward system, which can be 'compensated' by the intake of different psychoactive drugs. Hence, animals showing propensity for developing dependence to a specific drug class may also be useful for modeling other addictions. We compared the effects of repeated (14 daily doses) morphine (10 mg/kg) or methadone (2 mg/kg) treatment followed by a 2-week withdrawal and a morphine challenge (5 mg/kg) on locomotor activity, brain Fos expression and selected brain regional levels of dopamine, serotonin and their metabolites in the 38th generations of selectively bred Warsaw low-alcohol-preferring (WLP) and Warsaw high-alcohol-preferring (WHP) rat lines. The rats were given the opioids during the active (i.e. dark) phase of their daily cycle. Drug-naive WHP rats compared to their WLP counterparts showed higher locomotor activity in an open field test and higher propensity for lasting behavioral sensitization to morphine. Morphine did not significantly enhance, but suppressed Fos expression in certain brain regions of drug-naive WLP and WHP rats. Fos expression revealed considerable differences in the responses of WLP and WHP rats to morphine challenge, particularly after methadone pretreatment These differences were associated with differences in monoamine metabolite levels that were suggestive of elevated basal ganglia and lowered frontal cortical dopamine function, and of lowered somatosensory cortex serotonin function, in the morphine-challenged WHP rats (irrespective of the pretreatment type). Hence, the WLP/WHP line pair may be useful for the search of factors that underlie the propensity for developing opiate dependence.

• 出版日期2011-3-30