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

Abstract

The steady state levels of the messenger RNA (mRNA) of eight GABA(A) receptor subunits, five 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. 'Behavioural dependence' including loss of control was induced by offering 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 fluid over a 9-month period (also not 'behaviourally dependent', Group C) and ethanol-naive control rats (Group D). All groups were sacrificed 1 month after the ethanol was withdrawn. The mRNA concentrations of all eight GABA receptor subunits, four out of the five subunits of different 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. 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 effect than after forced administration. 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 specifically associated with 'behavioural dependence'.

Figure 1

Steady-state mRNA concentrations of GABA₂ receptor subunits in the parieto-occipital cortex in the four experimental groups.

Figure 2

Steady-state mRNA concentrations of glutamate receptor subunits in the parieto-occipital cortex in the four experimental groups.

Figure 3

Steady-state mRNA concentrations of the kainate 2 receptor in seven brain regions in four experimental groups.

Figure 4

Steady-state mRNA concentrations of glutamate decarboxylase 65 in eight brain regions in four experimental groups.

Figure 5

Steady-state mRNA concentrations of enzymes involved in glutamate and GABA production and recycling in the parieto-occipital cortex in four experimental groups.

Figure 6

Steady-state mRNA concentrations of cytochrome oxidase subunits, ATP synthetase subunits and Na⁺/K⁺ ATPase subunits in the parieto-occipital cortex in the four experimental groups.