The function of γ‐aminobutyric acid (GABA)ergic systems in response to acute and repeated stressful manipulations was evaluated in both the corpus striatum and frontal cerebral cortex of the rat.
In the corpus striatum the activity of the synthetic enzyme for GABA (glutamic acid decarboxylase, GAD) and the levels of GABA were reduced by acute immobilization stress (1 h). GABA turnover was reduced only by acute cold stress (3 h, 4°C).
In the frontal cerebral cortex no changes were observed after acute stressful manipulations, but repeated stress (0.5 h immobilization per day for 14 days) enhanced both GAD activity and GABA turnover, and reduced GABA levels.
In conclusion, it would appear that the GABAergic system in the corpus striatum of the rat is most sensitive to acute stress and that the system in the frontal cerebral cortex area is preferentially responsive to chronic stress. It is speculated that the cortical GABAergic system is responsible for adaptive responses to the adverse conditions prevailing during chronic stress.
The acute (1 h, i.p.) and chronic (14 days, p.o.) effects of LiCl treatment upon GABA-ergic neurons were studied in the rat corpus striatum and frontal cerebral cortex. One hour after a single injection of LiCl the activity of glutamic acid decarboxylase (GAD) was reduced by 29% in the striatum (2 meq/kg LiCl) and by 38% in the cerebral cortex (10 meq/kg LiCl). In contrast, striatal GAD was activated by 34% 1 h after the injection of 10 meq/kg of LiCl; this dose also reduced the endogenous striatal GABA level by 24%. After 14 days of oral LiCl administration (2 meq/kg/day): a) cortical GAD activity was enhanced by 50% and GABA concentration was decreased by 28%; b) no changes were observed in the striatum. These findings suggest that: LiCl administration stimulates GABA-ergic function in specific areas (depending on the dose and length of treatment) increasing both GAD activity and probably GABA release. This occurs in the striatum after acute treatment only with a high dose, and in the frontal cerebral cortex after chronic treatment with a low dose.
Lithium chloride was given to rats i.p. at single doses of 2 and 10 meq/kg, respectively. It produced a suppression of motor activity and an increase in the dopamine content of the striatum. The magnitude of these effects were dose- and time-dependent as well as transient in nature. After 60 min of injection, the higher dose (10 meq/kg) reduced motor activity by 67% and increased striatal dopamine content by 56% while the lower dose (2 meq/kg) reduced motor activity by 42% and elevated striatal dopamine by 36%. These effects vanished 24 h after administration regardless the dose employed. None of the two doses of LiCl altered either dopamine biosynthesis in vivo (measured as the accumulation of a precursor of synthesis after decarboxylase inhibition), or the activity of tyrosine hydroxylase ex vivo under subsaturating conditions (i.e. enzyme activity in the tissues obtained from the animals post mortem). An increased deamination of tyramine by monoamineoxidase (MAO) was found in striatal homogenates after 60 min of the injection of 2 or 10 meq/kg of LiCl. This was due to a lower Km for the substrate as revealed by kinetic studies. LiCl treatment did not change the proportion of MAO A:B. As neither dopamine synthesis was increased nor the activity of the catabolic enzyme MAO was reduced (but it was oppositely enhanced), the increment in striatal dopamine content might have likely resulted from a reduced release and/or an increased amine reuptake by the neurons. We postulate that the reduced motor activity observed shortly after injection of LiCl would be related to an interference with striatal dopaminergic neurotransmission.
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