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Changes in γ‐aminobutyric acid and glutamic acid decarboxylase in discrete regions of rat brain following lithium administration and withdrawal
Author(s) -
Ahluwalia Pardeep,
Grewaal Darshan S.,
Singhal Radhey L.
Publication year - 1983
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430030206
Subject(s) - pons , aminooxyacetic acid , glutamate decarboxylase , endocrinology , midbrain , striatum , medicine , chemistry , medulla , hypothalamus , dopamine , biology , central nervous system , biochemistry , enzyme
Abstract The influence of low dose (1 mmol/kg/day) chronic lithium (Li) treatment was studied on γ‐aminobutyric acid (GABA) levels and glutamic acid decarboxylase (GAD) activity in discrete regions of rat brain. In Li‐treated animals, GABA levels of striatum, midbrain, and ponsmedulla were significantly elevated in comparison to controls. Following 2 days of withdrawal from Li, GABA remained significantly higher in midbrain and pons‐medulla, but returned to control values in striatum. Administration of aminooxyacetic acid (AOAA) 1 hr prior to sacrifice produced an approximately twofold increase in regional GABA content in all three experimental groups. The activity of GAD was enhanced in striatum (11%) and pons‐medulla (22%), but decreased slightly in midbrain (5%) of Li‐treated animals. Li withdrawal caused a significant reduction in GAD activity of hypothalamus and pons‐medulla when compared to control or Li‐treated rats. Acute injection of AOAA enhanced GAD activity in midbrain of the Li‐treated animals and hypothalamus of the Li‐withdrawal group. Our data demonstrate that long‐term Li administration and its subsequent withdrawal has differential effects on both GABA and GAD in various regions of rat brain. However, whether these changes brought about by Li are due to its direct effect, or are exerted indirectly through other neurotransmitter systems, needs to be clarified.