The modulatory effects of high affinity GABA B receptor antagonists in an active avoidance learning paradigm in rats

Getova, D.; Bowery, Norman G.

doi:10.1007/s002130050632

Cited by 49 publications

(20 citation statements)

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“…Whether the two deficits have the same underlying GABA pathology remains speculative. Animal studies suggest that cognitive symptoms may benefit from GABA A agonists and GABA B antagonists, [22][23][24][25][26][27] similar to the positive schizophrenia symptoms. With no human trials at hand, it is difficult to predict with confidence the impact of GABAergic treatment on the cognitive symptoms of schizophrenia.…”

Section: Benzodiazepinesmentioning

confidence: 96%

“…Future development of GABA B antagonists will hopefully continue as these agents have had promising results in improving cognitive performance in animal models in a limited number of preliminary studies. [22][23][24][25][26][27] These agents also may be effective in the treatment of absence seizures, 28 although this effect seems to be dose-dependent as they can be proconvulsive at higher doses. 29,30 Other studies suggest their theoretical potential for treatment of anxiety, 31 and Parkinson disease, 32 although the evidence is currently limited.…”

Section: Impact Of Gaba a Subunit Composition On Receptor Functionmentioning

confidence: 97%

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GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

Wassef¹,

Baker

Kochan

2003

Journal of Clinical Psychopharmacology

223

148

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Alterations in the GABA neurotransmitter system are found in clinical and basic neuroscience schizophrenia studies as well as animal models and may be involved in the pathophysiology of schizophrenia. The interaction of GABA with other well-characterized neurotransmitter abnormalities remains to be understood. Future studies should elucidate the potential therapeutic role for GABA ligands in schizophrenia treatment.

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Section: Benzodiazepinesmentioning

confidence: 96%

Section: Impact Of Gaba a Subunit Composition On Receptor Functionmentioning

confidence: 97%

GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

Wassef¹,

Baker

Kochan

2003

Journal of Clinical Psychopharmacology

223

148

View full text Add to dashboard Cite

show abstract

“…They can either enhance (Getova and Bowery, 1998;Nakagawa et al, 1999;Stäubli et al, 1999;Getova and Bowery, 2001) or attenuate (Brucato et al, 1996) cognitive performance in a variety of learning paradigms in mice and rats. We reported previously that GABA B(1) Ϫ/Ϫ mice exhibit a severe impairment of passive avoidance learning .…”

Section: Gaba B(2)mentioning

confidence: 99%

Redistribution of GABA_B(1)Protein and Atypical GABA_BResponses in GABA_B(2)-Deficient Mice

Gassmann¹

2004

J. Neurosci.

218

155

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GABA B receptors mediate slow synaptic inhibition in the nervous system. In transfected cells, functional GABA B receptors are usually only observed after coexpression of GABA B(1) and GABA B(2) subunits, which established the concept of heteromerization for G-proteincoupled receptors. In the heteromeric receptor, GABA B(1) is responsible for binding of GABA, whereas GABA B(2) is necessary for surface trafficking and G-protein coupling. Consistent with these in vitro observations, the GABA B(1) subunit is also essential for all GABA B signaling in vivo. Mice lacking the GABA B(1) subunit do not exhibit detectable electrophysiological, biochemical, or behavioral responses to GABA B agonists. However, GABA B(1) exhibits a broader cellular expression pattern than GABA B(2) , suggesting that GABA B(1) could be functional in the absence of GABA B(2) . We now generated GABA B(2) -deficient mice to analyze whether GABA B(1) has the potential to signal without GABA B(2) in neurons. We show that GABA B(2) Ϫ/Ϫ mice suffer from spontaneous seizures, hyperalgesia, hyperlocomotor activity, and severe memory impairment, analogous to GABA B(1) Ϫ/Ϫ mice. This clearly demonstrates that the lack of heteromeric GABA B(1,2) receptors underlies these phenotypes. To our surprise and in contrast to GABA B(1) Ϫ/Ϫ mice, we still detect atypical electrophysiological GABA B responses in hippocampal slices of GABA B(2) Ϫ/Ϫ mice. Furthermore, in the absence of GABA B(2) , the GABA B(1) protein relocates from distal neuronal sites to the soma and proximal dendrites. Our data suggest that association of GABA B(2) with GABA B(1) is essential for receptor localization in distal processes but is not absolutely necessary for signaling. It is therefore possible that functional GABA B receptors exist in neurons that naturally lack GABA B(2) subunits.

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“…Studies have reported enhanced learning and memory after the administration of several GABA B antagonists (Castellano et al, 1993; Getova & Bowery, 1998); however, these results are not uniform. For instance, Mondadori, Mobius, & Borkowski (1996) administered a GABA B antagonist, CGP 36742, after a passive avoidance task and found that the compound enhanced memory for the task.…”

Section: Introductionmentioning

confidence: 96%

Baclofen administration alters fear extinction and GABAergic protein levels

Heaney

Bolton

Murtishaw

et al. 2012

Neurobiology of Learning and Memory

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The investigation of GABAergic systems in learning and extinction has principally focused on ionotropic GABAA receptors. Less well characterized is the metabotropic GABAB receptor, which when activated, induces a more sustained inhibitory effect and has been implicated in regulating oscillatory activity. Few studies have been carried out utilizing GABAB ligands in learning, and investigations of GABAB in extinction have primarily focused on interactions with drugs of abuse. The current study examined changes in GABAB receptor function using the GABAB agonist baclofen (2mg/mL) or the GABAB antagonist phaclofen (0.3mg/mL) on trace cued and contextual fear conditioning and extinction. The compounds were either administered during training and throughout extinction in Experiment 1, or starting 24 hours after training and throughout extinction in Experiment 2. All drugs were administered 1mL/kg via intraperitoneal injection. These studies demonstrated that the administration of baclofen during training and extinction trials impaired animals’ ability to extinguish the fear association to the CS, whereas the animals that were administered baclofen starting 24 hours after training (Experiment 2) did display some extinction. Further, contextual fear extinction was impaired by baclofen in both experiments. Tissue analyses suggest the cued fear extinction deficit may be related to changes in the GABAB2 receptor subunit in the amygdala. The data in the present investigation demonstrate that GABAB receptors play an important role in trace cued and contextual fear extinction, and may function differently than GABAA receptors in learning, memory, and extinction.

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The modulatory effects of high affinity GABA B receptor antagonists in an active avoidance learning paradigm in rats

Cited by 49 publications

References 12 publications

GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

Redistribution of GABA_B(1)Protein and Atypical GABA_BResponses in GABA_B(2)-Deficient Mice

Baclofen administration alters fear extinction and GABAergic protein levels

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The modulatory effects of high affinity GABA B receptor antagonists in an active avoidance learning paradigm in rats

Cited by 49 publications

References 12 publications

GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

Redistribution of GABAB(1)Protein and Atypical GABABResponses in GABAB(2)-Deficient Mice

Baclofen administration alters fear extinction and GABAergic protein levels

Contact Info

Product

Resources

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Redistribution of GABA_B(1)Protein and Atypical GABA_BResponses in GABA_B(2)-Deficient Mice