Lack of Beneficial Effects of L-Baclofen in Affective Disorder
ABSTRACT GABAB mechanisms have been implicated in the antinociceptive, but not anticonvulsant effects of carbamazepine. A variety of antidepressants have been reported to upregulate GABAB receptors after chronic administration. The GABAB agonist l-baclofen was studied in depressed patients based on two separate rationales. l-Baclofen, in doses ranging from 10-55 mg/day, was administered to five patients with primary affective disorder. No patient showed a positive clinical response, while three patients showed a pattern of increasing depression or cycling during treatment and improvement during withdrawal. These preliminary data suggest that GABAB agonism is unlikely to produce antidepressant effects and may be unrelated to the mechanism of carbamazepine's antidepressant action. These data, taken with a reinterpretation of other findings that antidepressant modalities upregulate GABAB receptors in brain following chronic administration, suggest that GABAB antagonism rather than agonism may be a fruitful clinical strategy to explore in depression.
- SourceAvailable from: S.Hossein Fatemi
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- "GABA B receptor antagonists have been found to produce antidepressant properties in animal models, as have GABBR1 deletion studies (Nakagawa et al., 1999; Heese et al., 2000; Mombereau et al., 2005). Moreover, a study found that treatment of subjects with major depression with baclofen resulted in a worsening of symptoms (Post et al., 1991). These findings have led some to believe that an overactive GABA system contributes to major depression (Ghose et al., 2011). "
ABSTRACT: Postmortem and genetic studies have clearly demonstrated changes in GABA(B) receptors in neuropsychiatric disorders such as autism, bipolar disorder, major depression, and schizophrenia. Moreover, a number of recent studies have stressed the importance of cerebellar dysfunction in these same disorders. In the current study, we examined protein levels of the two GABA(B) receptor subunits GABBR1 and GABBR2 in lateral cerebella from a well-characterized cohort of subjects with schizophrenia (n=15), bipolar disorder (n=14), major depression (n=13) and healthy controls (n=12). We found significant reductions in protein for both GABBR1 and GABBR2 in lateral cerebella from subjects with schizophrenia, bipolar disorder and major depression when compared with controls. These results provide further evidence of GABAergic dysfunction in these three disorders as well as identify potential targets for therapeutic intervention.Schizophrenia Research 02/2011; 128(1-3):37-43. DOI:10.1016/j.schres.2010.12.025 · 4.43 Impact Factor
Conference Paper: Computing characteristic views of quadric-surfaced solids[Show abstract] [Hide abstract]
ABSTRACT: An algorithm is presented for computing the characteristic views (CVs) of quadric-surfaced solids. The CVs are determined by analyzing the characteristic-view domains of the object by relating changes in the topology of the object's line structure to changes in the occlusion of 3D edges. The main task of the algorithm is to compute the envelope boundaries for viewpoint regions for which the object's visible-line projections have topologically equivalent line-junction graphs. By using the concepts of generalized edge, generalized face, and generalized vertex and using the techniques of order-of-visibility propagation and edge classification, the algorithm can efficiently compute both local and global visibility of edge segments, and therefrom compute the required envelope boundaries. This algorithm is shown to hold for quadric-surfaced solids in general and to treat a polyhedral object as a special casePattern Recognition, 1990. Proceedings., 10th International Conference on; 07/1990
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ABSTRACT: There are two gamma-aminobutyric acid (GABA) hypotheses of the antidepressants action: an increase in GABAA neurotransmission or a decrease in GABAB neurotransmission may contribute to action of antidepressants. In this study, involvement of GABAA and GABAB receptor systems was examined in the learned helplessness paradigm in rats. Rats were injected with bicuculline or baclofen for 14 days. On day 14, the rats were subjected to 15 inescapable shocks. On day 15, they underwent the 40-trial escape test. Baclofen exacerbated the escape failures in the rats subjected to the inescapable shocks, although baclofen had no effects in the animals without shock pre-treatment. Bicuculline failed to influence the escape failures in the rats with the 15-shock pre-treatment. These results suggest that the long-term increase in GABAB neurotransmission but not the long-term attenuation of GABAA neurotransmission may be related to helplessness in rats.Brain Research 12/1996; 741(1-2):240-5. DOI:10.1016/S0006-8993(96)00929-8 · 2.83 Impact Factor