Chronic binge‐like moderate ethanol drinking in rats results in widespread decreases in brain serotonin, dopamine, and norepinephrine turnover rates reversed by ethanol intake

Abstract

This research was initiated to assess the turnover rates (TORs) of dopamine (DA), norepinephrine (NA), serotonin (5-HT), aspartate, glutamate, and GABA in brain regions during rodent ethanol/sucrose (EtOH) and sucrose (SUC) drinking and in animals with a history of EtOH or SUC drinking to further characterize the neuronal systems that underlie compulsive consumption. Groups of five male rats were used, with two trained to drink EtOH solutions, two to drink SUC and one to serve as a non-drinking control. When stable drinking patterns were obtained, rats were pulse labeled intravenously and killed 60 or 90 min later and the TORs of DA, norepinephrine, 5-HT, aspartate, glutamate, and GABA determined in brain regions. Changes in the TOR of 5-HT, DA, and NA were detected specific to EtOH drinking, SUC drinking or a history of EtOH or SUC drinking. An acute EtOH deprivation effect was detected that was mostly reversed with EtOH drinking. These results suggest that binge-like drinking of moderate amounts of EtOH produces a deficit in neuronal function that could set the stage for the alleviation of anhedonic stimuli with further EtOH intake that strengthen EtOH seeking behaviors which may contribute to increased EtOH use in at risk individuals.

αCaMKII Autophosphorylation Controls the Establishment of Alcohol Drinking Behavior

“…This is in line with Het behavior in that they drop back to low consumption after two withdrawals (Figure 1c). Deficiencies in brain 5-HT levels and turnover have previously been associated with high alcohol drinking (Murphy et al, 1982;Virkkunen and Linnoila, 1997;Smith et al, 2008). Conversely, artificially induced increases in extracellular 5-HT levels can reduce alcohol drinking (Boyce-Rustay et al, 2006).…”

A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

“…Research on the involvement of 5-HT in binge alcohol drinking has been limited, with some evidence that binge drinking induces a blunted 5-HT response in the Scheduled High Alcohol Consumption (SHAC) mouse binge drinking model (Szumlinski et al, 2007). Additionally, acute withdrawal from alcohol after binge-like exposure leads to a wide-spread reduction in 5-HT and other neurotransmitters in several brain regions including those associated with the mesocorticolimbic system (Smith, Co, Mcintosh, & Cunningham, 2008). In general, these findings indicate that serotonergic treatments may disrupt binge alcohol drinking and may interfere with the progression to alcohol dependence, in certain individuals.…”

Effects of a single high dose of Chlorpyrifos in long-term feeding, ethanol consumption and ethanol preference in male Wistar rats with a previous history of continued ethanol drinking

“…Moreover, both dopaminergic and cannabinoid system have a key role in voluntary ethanol intake (Casu et al, 2002;Colombo et al, 2002;Erdozain and Callado, 2011;Samson et al, 2002). In this regard, several studies showed that chronic exposure to alcohol as the administration of CPF lead to decreased levels of dopamine (Gralewitz et al, 2002;Moreno et al, 2008;Smith et al, 2008) and increased levels of endocannabinoids Liu et al, 2013;Quistad et al, 2001Quistad et al, , 2002. Thus, pharmacological manipulations that trigger a decrease in dopamine levels (Izco et al, 2007;Olive et al, 2002;Rassnick et al, 1999) or increased levels of endocannabinoids Erdozain and Callado, 2011) cause an increase in ethanol consumption.…”

“…In the present study, the effect of CPF on the ethanol consumption is mediated by prior exposure to alcohol in the case of pre-exposed animals. Therefore, chronic ethanol exposure may be affecting neurochemical systems as the dopaminergic or GABAergic (Diaz et al, 2011;Smith et al, 2008), and/or neuromodulators such as the cannabinoid system (Basavarajappa and Hungund, 1999;Basavarajappa et al, 2000) that are also neurobiological targets of CPF. Moreover, both dopaminergic and cannabinoid system have a key role in voluntary ethanol intake (Casu et al, 2002;Colombo et al, 2002;Erdozain and Callado, 2011;Samson et al, 2002).…”

“…Additionally, several studies showed that chron--els of dopamine (Corominas et al, 2007;Smith et al, 2008) and increased levels of endocannabinoids (Basavarajappa and Hungund, 1999;Basavarajappa et al, 2000;Colombo et al, 2002). Besides, levels of orexin mRNA (Morgansterm et al et al, 2010) were reduced and levels of opioid encephalin and galanin were increased (Chang et al, 2007 by chronic exposure to ethanol.…”