Gene expression of receptors and enzymes involved in GABAergic and glutamatergic neurotransmission in the CNS of rats behaviourally dependent on ethanol

Abstract

1 The steady state levels of the messenger RNA (mRNA) of eight GABA A receptor subunits, ®ve glutamate receptor subunits and seven enzymes involved in the synthesis of glutamate and GABA were measured in eight regions of rat brain in a recently developed animal model of`behavioural dependence' on ethanol. 2`Behavioural dependence' including loss of control was induced by o ering the rats the choice between ethanol and water over a 9-month period (Group A). This group was compared with a group given the choice between ethanol and water for only 2 months (not yet`behaviourally dependent', Group B), a group forced to consume ethanol as sole¯uid over a 9-month period (also not`behaviourally dependent', Group C) and ethanol-naive control rats (Group D). All groups were sacri®ced 1 month after the ethanol was withdrawn. 3 The mRNA concentrations of all eight GABA receptor subunits, four out of the ®ve subunits of di erent glutamate receptors and those of seven enzymes involved in GABA and glutamate production were reduced almost exclusively in the parieto-occipital cortex in Groups A and B, but not Group C. 4 These data suggest that the synthesis of glutamate and GABA and the activities of their respective neurons are selectively impaired in the parieto-occipital cortex in the groups having consumed ethanol in a free-choice design, in which its rewarding properties can better take e ect than after forced administration. 5 As the parieto-occipital cortex is believed to contain emotional memory structures, it may be hypothesized that the glutamatergic and GABAergic neuronal systems in this area are involved in the development of memory for reward from ethanol. However, they are not speci®cally associated with`behavioural dependence'.

The efficacy of a low dose combination of topiramate and naltrexone on ethanol reinforcement and consumption in rat models

“…To most accurately model the chronic exposure that is characteristic of human AUDs, we began treatments after a minimum of 6 months of ethanol experience. Prolonged access, defined in previous studies with ethanol experience ranging from 2–16 months, is associated with neurological changes that affect GABA, glutamate, and opioid receptor function (Eravci et al 2000; Darstein et al 1998; Hölter et al 2000). …”

Alcohol preferring (P) rats as a model for examining sex differences in alcohol use disorder and its treatment

“…As the targets of these treatments (i.e. GABA, glutamate, and opioid receptor) are altered over the course of chronic alcohol use, this model of prolonged access may also be more neurobiologically relevant (Eravci et al 2000; Darstein et al 1998; Hölter et al 2000). …”

Associations of glutamate decarboxylase genes with initial sensitivity and age-at-onset of alcohol dependence in the Irish Affected Sib Pair Study of Alcohol Dependence

“…Mice and rat studies have shown that GAD genes expression was altered during diazepam withdrawal (Izzo et al, 2001), alcohol withdrawal or dependence (Eravci et al, 2000), or chronic exposure to high-dose methamphetamine (Zhang et al, 2006). However, the evidence of expression alteration of GAD genes is not consistent (Fehr et al, 2003), and gene expression levels appear to vary by brain region in response to drug treatment.…”