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Nylander I1, Granholm L1, Segerström L1, Palm S1

1 Neuropharmacology, Addiction & Behaviour, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
Abundant evidence support close interactions between alcohol and endogenous opioids and also between alcohol, opioids and dopamine. For example, alcohol affects opioid peptides and receptors and, vice versa, opioid receptor agonists and antagonists modulate alcohol intake and alcohol-induced dopamine responses in experimental and clinical studies. However, despite many studies on alcohol-induced effects on endogenous opioids, there is no consensus regarding the impact of alcohol on endogenous opioids and the exact nature of the alcohol-opioid link remains unclear. Further, even though alcohol consumption is common in adolescence, the impact of alcohol exposure on the young developing brain is largely unknown. Effects of adolescent alcohol exposure were studied in Wistar rats after either voluntary drinking in different housing conditions or passive intragastric administration of alcohol, alone and in combination with nicotine. The rats were exposed to episodic alcohol with three days of exposure and four drug-free days in-between. Age-specific housing- and alcohol-induced effects were noted for dynorphin, enkephalin and beta-endorphin. Voluntary drinking in adolescence affected many brain regions and some of these effects were independent on housing while effects especially in the amygdala were sensitive to housing conditions. Intragastric adolescent alcohol exposure resulted in another effect profile and simultaneous nicotine exposure was found to modulate these alcohol-induced effects. Measurements of dopamine release and reuptake using in vivo chronoamperometry revealed that adolescent voluntary drinking, but not passive administration of alcohol, affected basal striatal dopamine dynamics in adulthood. Further, adolescent alcohol exposure was associated with altered adult response to another drug of abuse, i.e. amphetamine. The results provide new insight into the consequences of adolescent alcohol exposure on endogenous opioids and dopamine, and highlight confounding factors that may contribute to the existing incoherent picture of alcohol-opioid interactions in the literature.