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Lloyd KG, Thuret F, Pilc A. Upregulation of gamma-aminobutyric acid (GABA) B binding sites in rat frontal cortex: a common action of repeated administration of different classes of antidepressants and electroshock. J Pharmacol Exp Ther 235: 191-199

Journal of Pharmacology and Experimental Therapeutics (Impact Factor: 3.86). 11/1985; 235(1):191-9.
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ABSTRACT The action of different classes of clinically effective antidepressants and electroshock on gamma-aminobutyric acid (GABA) B recognition sites in the frontal cortex was compared to that of other psychotropic agents. After either prolonged (6-18 days) s.c. infusion via osmotic minipumps or repeated i.p. injections of different antidepressants, or a series of electroshocks, treatment was halted and 72 hr later the animals were sacrificed, the brain was dissected and frozen. All major antidepressants (desipramine, amitryptyline or maprotiline), several newer compounds with reported antidepressant activity (viloxazine, zimelidine, fluoxetine, citalopram, progabide, fengabine, sodium valproate, mianserin, trazodone or nomifensine) as well as pargyline and repeated electroshocks, up-regulated GABA B binding in the rat frontal cortex but not hippocampus. This appeared to be a maximum binding effect, but in some instance the kinetics were more complex. Reserpine, diphenylhydantoin and phenobarbital down-regulated GABA B binding in the frontal cortex, whereas this was unaltered by haloperidol, chlorpromazine or diazepam administration. Desipramine up-regulated GABA B binding in a dose- and time-dependent manner (minimum effective dose, 1.25 mg/kg/day s.c. for 18 days; onset of action, 6 days at 5 mg/kg/day s.c.). Together with the rather sparse data in the literature on GABA in depression and antidepressant drug action, these findings support a common GABAergic mechanism of action of antidepressant drugs and electroshock, mediated via GABA B synapses.

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    • "A role for the amino-acid neurotransmitter, g-aminobutyric acid (GABA), in mood disorders was first proposed over 20 years ago by Emrich et al. (1980), based on the clinical observation that valproic acid, a GABA agonist, was effective in the treatment of bipolar patients. The studies of Lloyd and colleagues showing an upregulation of GABA B receptors after prolonged antidepressant treatment in rats (Pilc and Lloyd, 1984; Lloyd et al., 1985) focused attention on this receptor type. GABA is the major inhibitory neurotransmitter in the central nervous system (Paredes and Agmo, 1992), acting via stimulation of GABA A , GABA B and GABA C receptors (Chebib and Johnston, 1999; Bormann, 2000; Rudolph et al., 2001). "
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    • "Ž upregulated by administration of antidepressants Lloyd et . al., 1985 . GABA has been shown to play a role in Ž . depression Petty et al., 1995a,b . We had also shown that Ž . a GABA receptor mechanism s may modulate antidepres- Ž . sant-induced antinociception Sabetkasai et al., 1999 . Antidepressants are probably the most commonly prescribed Ž . drugs for the treatment of chronic pain Feinmann, 1985 . Ž"
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    • "Using clonidine as the pharmacological probe, studies on Cx2-receptor functioning have been conducted on rats and have indicated that TCP and PLZ both cause a down-regulation of cX2-adrenergic receptors after chronic administration (Greenshaw et al 1988; McKenna et al 1992a). Lloyd et al (1985) reported an up-regulation of GABAB receptors in the frontal cortex ofrats after chronic administration of the MAO inhibitor pargyline, but McManus and Greenshaw (199la; 199 lb) reported that PLZ did not affect GABAB receptor density or functioning, as measured in neurochemical and behavioral experiments, respectively. The chronic administration of both PLZ and TCP has been reported to cause a decrease in the density of 3H-tryptamine binding sites in the brains of rats (Mousseau et al, in press). "
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