Anxiolytic-like effect of the GABA-transaminase inhibitor vigabatrin (gamma-vinyl GABA) on rat exploratory activity

Sherif, Fathi M; Harro, Jaanus; El-Hwuegi, Abdulla; Oreland, Lars

doi:10.1016/0091-3057(94)90226-7

Cited by 37 publications

(15 citation statements)

References 19 publications

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“…These data show a significant improvement of explorative behaviour with vigabatrin in socially isolated rats using the elevated plus maze and the open field test after administration of vigabatrin (Sherif et al 1994;Sherif and Oreland 1995;Sayin et al 1992). Moreover, this finding is in line with effects of other GABAergic agents in humans.…”

Section: Discussionsupporting

confidence: 76%

“…Sherif and colleagues investigated the effects of GABA-transaminase inhibition on exploratory behaviour in socially isolated rats using both the elevated plus maze and the open field NO . 5 test (Sherif et al 1994;Sherif and Oreland 1995). Despite these promising results in animal models it is still unclear whether vigabatrin exerts anxiolytic properties also in humans.…”

Section: Vigabatrin Increases Gamma Aminobutyric Acid (Gaba) Levels Bmentioning

confidence: 99%

“…Sayin et al (1992) compared the anxiolytic effects of diazepam and vigabatrin in rats and found a significant decrease of anxiety with both substances using the elevated plus maze test. Sherif and colleagues investigated the effects of GABA-transaminase inhibition on exploratory behaviour in socially isolated rats using both the elevated plus maze and the open field test (Sherif et al 1994;Sherif and Oreland 1995). Despite these promising results in animal models it is still unclear whether vigabatrin exerts anxiolytic properties also in humans.…”

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confidence: 99%

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Vigabatrin Decreases Cholecystokinin-Tetrapeptide (CCK-4) Induced Panic in Healthy Volunteers

Zwanzger

Baghai

Schuele

et al. 2001

Neuropsychopharmacology

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Vigabatrin increases gamma aminobutyric acid (GABA) levels by irreversible inhibition of the GABA-catabolizing enzyme GABA-transaminase (GABA-T). Preclinical studies suggest anxiolytic effects in vigabatrin treated rats. Anxiolytic effects in patients with panic disorder (PD) could therefore be expected. To evaluate putative anxiolytic properties of vigabatrin in humans, CCK-4-induced panic symptoms were studied in healthy volunteers before and after vigabatrin treatment. After placebo-controlled administration of 50 g CCK-4, ten healthy volunteers received vigabatrin for seven days with a daily dosage of 2 g. The treatment period was followed by a second CCK-4 challenge. Panic and anxiety were assessed using the Acute Panic Inventory (API) score and a DSM-IV derived panicsymptom-scale (PSS). ACTH and cortisol plasma levels were determined during the CCK-4 challenge. All subjects reported a marked reduction of CCK-4-induced panic symptoms and anxiety after seven days of vigabatrin treatment both in the API-and PSS-scores. MoreoverThe new antiepileptic drug vigabatrin is a selective irreversible inhibitor of GABA-transaminase (GABA-T), the main degradative enzyme of GABA (Harden 1994). Vigabatrin increases CSF GABA levels by 2 to 3-fold when administered in anticonvulsant doses (Ben-Menachem 1989). Preclinical studies suggest that vigabatrin has anxiolytic properties in addition to its anticonvulsant effects. Sayin et al. (1992) compared the anxiolytic effects of diazepam and vigabatrin in rats and found a significant decrease of anxiety with both substances using the elevated plus maze test. Sherif and colleagues investigated the effects of GABA-transaminase inhibition on exploratory behaviour in socially isolated rats using both the elevated plus maze and the open field NO . 5 test (Sherif et al. 1994;Sherif and Oreland 1995). Despite these promising results in animal models it is still unclear whether vigabatrin exerts anxiolytic properties also in humans.CCK-4 has potent anxiogenic properties both in patients with panic disorder and in healthy volunteers (Bradwejn et al. 1990;Bradwejn et al. 1991a;Bradwejn et al. 1991b). Recent data suggest that CCK-4-induced panic is attenuated by antipanic treatment. A decrease of the anxiogenic effects of CCK-4 has been shown after treatment with benzodiazepines in healthy volunteers (de Montigny 1989). Moreover, antidepressants that are commonly used as antipanic treatment, e.g. imipramine (Bradwejn and Koszycki 1994a), fluvoxamine (van Megen etal. 1997) and citalopram (Shlik et al. 1997) reduced CCK-4-induced panic in patients with panic disorder.CCK-4-induced panic appears to be a suitable model to assess anxiolytic properties of psychopharmacological drugs in humans. To evaluate the putative anxiolytic properties of the selective GABA transaminase inhibitor vigabatrin, we therefore studied the effects of treatment with vigabatrin for seven days on CCK-4-induced panic symptoms in healthy male volunteers. METHODSTen male healthy volunteers (mean age ϭ 30.7 years, S...

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Section: Discussionsupporting

confidence: 76%

Section: Vigabatrin Increases Gamma Aminobutyric Acid (Gaba) Levels Bmentioning

confidence: 99%

mentioning

confidence: 99%

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Vigabatrin Decreases Cholecystokinin-Tetrapeptide (CCK-4) Induced Panic in Healthy Volunteers

Zwanzger

Baghai

Schuele

et al. 2001

Neuropsychopharmacology

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“…The compound has been shown to reduce anxiety-related behavior in animal studies [Sherif et al, 1994]. Moreover, vigabatrin exerts substantial anxiolytic ef fects both in patients with panic disorder [Zwanzger et al, 2001a] and on CCK-4-induced panic symptoms in healthy volunteers [Zwanzger et al, 2001a,c].…”

Section: Introductionmentioning

confidence: 99%

Effects of tiagabine on cholecystokinin-tetrapeptide (CCK-4)-induced anxiety in healthy volunteers

et al. 2003

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There is increasing evidence that a dysregulation of the gamma-aminobutyric acid (GABA) system plays a role in the pathophysiology of panic disorder. Selective enhancement of GABAergic neurotransmission has been shown to improve anxiety in experimental animals and in patients with panic disorder. Tiagabine is an antiepileptic drug, which increases GABA via selective blockade of GABA reuptake. Apart from its anticonvulsant activity anxiolytic properties could therefore be suggested. To investigate the putative anxiolytic properties of the GABA reuptake blocker tiagabine, we studied the impact of tiagabine treatment on cholecystokinin tetrapeptide (CCK-4)-induced panic. Fifteen healthy volunteers received 15 mg tiagabine daily for 1 week. A CCK-4 challenge was performed before and after treatment. Panic was assessed using the API- and PSS-score. There was a marked improvement of CCK-4-induced panic after 1 week of treatment. Both API- and PSS-scores showed a significant reduction. Our results suggest anxiolytic properties of tiagabine in humans, which provide sufficient rationale to assess its putative anxiolytic effects in patients with panic disorder under controlled conditions.

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“…Modulation of both behavior and hippocampal peak theta frequency upon 40-Hz stimulation (Figs. 3 and 7C,respectively) are similar to the effects of systemic administration to rodents of diazepam and/or vigabatrin, two compounds that increase GABAergic activity in the CNS (Bouwman et al 2004(Bouwman et al , 2005Caudarella et al 1987;Kalueff and Tuohimaa 2005b;Monmaur 1981;Sherif et al 1994). Local GABA increases have been previously associated with DBS both in brain slices (Moser et al 2003) and in vivo (Hiller et al 2007;Liu et al 2012;Windels et al 2000Windels et al , 2003, supporting the speculation that homologous changes might have contributed to our results.…”

Section: Discussionmentioning

confidence: 60%

Frequency dependence of behavioral modulation by hippocampal electrical stimulation

Corte

Wei

Chernyy

et al. 2014

Journal of Neurophysiology

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Electrical stimulation offers the potential to develop novel strategies for the treatment of refractory medial temporal lobe epilepsy. In particular, direct electrical stimulation of the hippocampus presents the opportunity to modulate pathological dynamics at the ictal focus, although the neuroanatomical substrate of this region renders it susceptible to altering cognition and affective processing as a side effect. We investigated the effects of three electrical stimulation paradigms on separate groups of freely moving rats (sham, 8-Hz and 40-Hz sinewave stimulation of the ventral/intermediate hippocampus, where 8-and 40-Hz stimulation were chosen to mimic naturally occurring hippocampal oscillations). Animals exhibited attenuated locomotor and exploratory activity upon stimulation at 40 Hz, but not at sham or 8-Hz stimulation. Such behavioral modifications were characterized by a significant reduction in rearing frequency, together with increased freezing behavior. Logistic regression analysis linked the observed changes in animal locomotion to 40-Hz electrical stimulation independently of time-related variables occurring during testing. Spectral analysis, conducted to monitor the electrophysiological profile in the CA1 area of the dorsal hippocampus, showed a significant reduction in peak theta frequency, together with reduced theta power in the 40-Hz vs. the sham stimulation animal group, independent of locomotion speed (theta range: 4 -12 Hz). These findings contribute to the development of novel and safe medical protocols by indicating a strategy to constrain or optimize parameters in direct hippocampal electrical stimulation.

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Anxiolytic-like effect of the GABA-transaminase inhibitor vigabatrin (gamma-vinyl GABA) on rat exploratory activity

Cited by 37 publications

References 19 publications

Vigabatrin Decreases Cholecystokinin-Tetrapeptide (CCK-4) Induced Panic in Healthy Volunteers

Vigabatrin Decreases Cholecystokinin-Tetrapeptide (CCK-4) Induced Panic in Healthy Volunteers

Effects of tiagabine on cholecystokinin-tetrapeptide (CCK-4)-induced anxiety in healthy volunteers

Frequency dependence of behavioral modulation by hippocampal electrical stimulation

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