Abstract
Considerable evidence indicates that the metabolite of ethanol (EtOH), acetaldehyde, is biologically active. Acetaldehyde can be formed from EtOH peripherally mainly by alcohol dehydrogenase (ADH), and also centrally by catalase. EtOH and acetaldehyde show differences in their behavioral effects depending upon the route of administration. In terms of their effects on motor activity and motivated behaviors, when administered peripherally acetaldehyde tends to be more potent than EtOH but shows very similar potency administered centrally. Since dopamine (DA) rich areas have an important role in regulating both motor activity and motivation, the present studies were undertaken to compare the effects of central (intraventricular, ICV) and peripheral (intraperitoneal, IP) administration of EtOH and acetaldehyde on a cellular marker of brain activity, c-Fos immunoreactivity, in DA innervated areas. Male Sprague-Dawley rats received an IP injection of vehicle, EtOH (0.5 or 2.5 g/kg) or acetaldehyde (0.1 or 0.5 g/kg) or an ICV injection of vehicle, EtOH or acetaldehyde (2.8 or 14.0 μmoles). IP administration of EtOH minimally induced c-Fos in some regions of the prefrontal cortex and basal ganglia, mainly at the low dose (0.5 g/kg), while IP acetaldehyde induced c-Fos in virtually all the structures studied at both doses. Acetaldehyde administered centrally increased c-Fos in all areas studied, a pattern that was very similar to EtOH. Thus, IP administered acetaldehyde was more efficacious than EtOH at inducing c-Fos expression. However, the general pattern of c-Fos induction promoted by ICV EtOH and acetaldehyde was similar. These results are consistent with the pattern observed in behavioral studies in which both substances produced the same magnitude of effect when injected centrally, and produced differences in potency after peripheral administration.
Highlights
Ethanol (EtOH) is converted into acetaldehyde in many organs by the enzyme alcohol dehydrogenase (ADH) (Cohen et al, 1980)
The purpose of the present study was twofold: first, to compare the pattern of c-Fos induction after EtOH and its metabolite acetaldehyde were administered by two routes of administration that have been demonstrated to reveal differences in the potency between both drugs, and second, we chose to study brain areas with DArgic innervations because both drugs have demonstrated to have effects on motor activity and motivated behaviors regulated by DA
From the present study we can conclude that EtOH and acetaldehyde produce a general pattern of c-Fos induction in PREFRONTAL CORTEX (PFC), basal ganglia, and limbic areas, most of which have a substantial DA innervation (Fields, 2007; Ikemoto, 2007), at doses that are able to affect motor activity and motivated behaviors (Arizzi et al, 2003; Correa et al, 2003a,b; Arizzi-LaFrance et al, 2006; Chuck et al, 2006; McLaughlin et al, 2008)
Summary
Ethanol (EtOH) is converted into acetaldehyde in many organs by the enzyme alcohol dehydrogenase (ADH) (Cohen et al, 1980). EtOH crosses the blood brain barrier and is found in peripheral organs as well as in the brain (Eriksson and Sippel, 1977; Deitrich, 1987; Zimatkin, 1991). Of ALDH in capillary endothelium and surrounding astrocytes of the blood brain barrier (Sippel, 1974; Westcott et al, 1980; Zimatkin, 1991). An alternative source of acetaldehyde in the brain is the local intracerebral metabolism of EtOH by the enzyme catalase (Cohen et al, 1980; Aragon et al, 1992; Correa et al, 2012)
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