GABAergic modulation of the 40 Hz auditory steady-state response in a rat model of schizophrenia

Jenifer Vohs, R. Chambers, Giri P. Krishnan, Brian O'Donnell, Sarah Berg, Sandra Morzorati

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24 Citations (Scopus)

Abstract

Auditory steady-state auditory responses (ASSRs), in which the evoked potential entrains to stimulus frequency and phase, are reduced in magnitude in patients with schizophrenia, particularly at 40 Hz. While the neural mechanisms responsible for ASSR generation and its perturbation in schizophrenia are unknown, it has been hypothesized that the GABAA receptor subtype may have an important role. Using an established rat model of schizophrenia, the neonatal ventral hippocampal lesion (NVHL) model, 40-Hz ASSRs were elicited from NVHL and sham rats to determine if NVHL rats show deficits comparable to schizophrenia, and to examine the role of GABAA receptors in ASSR generation. ASSR parameters were found to be stable across time in both NVHL and sham rats. Manipulation of the GABAA receptor by muscimol, a GABAA agonist, yielded a strong lesiondrug interaction, with ASSR magnitude and synchronization decreased in NVHL and increased in sham rats. The lesionmuscimol interaction was blocked by a GABAA receptor antagonist when given prior to muscimol administration, confirming the observed interaction was GABAA mediated. Together, these data suggest an alteration involving GABAA receptor function, and hence inhibitory transmission, in the neuronal networks responsible for ASSR generation in NVHL rats. These findings are consistent with prior evidence for alterations in GABA neurotransmitter systems in the NVHL model and suggest the utility of this animal modelling approach for exploring neurobiological mechanisms that generate or modulate ASSRs.

Original languageEnglish
Pages (from-to)487-497
Number of pages11
JournalInternational Journal of Neuropsychopharmacology
Volume13
Issue number4
DOIs
StatePublished - May 2010

Fingerprint

Schizophrenia
GABA-A Receptors
Muscimol
GABA-A Receptor Agonists
GABA-A Receptor Antagonists
Evoked Potentials
gamma-Aminobutyric Acid
Neurotransmitter Agents

Keywords

  • 40 Hz
  • Auditory steady-state responses
  • GABA
  • Neonatal ventral hippocampal lesion
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

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title = "GABAergic modulation of the 40 Hz auditory steady-state response in a rat model of schizophrenia",
abstract = "Auditory steady-state auditory responses (ASSRs), in which the evoked potential entrains to stimulus frequency and phase, are reduced in magnitude in patients with schizophrenia, particularly at 40 Hz. While the neural mechanisms responsible for ASSR generation and its perturbation in schizophrenia are unknown, it has been hypothesized that the GABAA receptor subtype may have an important role. Using an established rat model of schizophrenia, the neonatal ventral hippocampal lesion (NVHL) model, 40-Hz ASSRs were elicited from NVHL and sham rats to determine if NVHL rats show deficits comparable to schizophrenia, and to examine the role of GABAA receptors in ASSR generation. ASSR parameters were found to be stable across time in both NVHL and sham rats. Manipulation of the GABAA receptor by muscimol, a GABAA agonist, yielded a strong lesiondrug interaction, with ASSR magnitude and synchronization decreased in NVHL and increased in sham rats. The lesionmuscimol interaction was blocked by a GABAA receptor antagonist when given prior to muscimol administration, confirming the observed interaction was GABAA mediated. Together, these data suggest an alteration involving GABAA receptor function, and hence inhibitory transmission, in the neuronal networks responsible for ASSR generation in NVHL rats. These findings are consistent with prior evidence for alterations in GABA neurotransmitter systems in the NVHL model and suggest the utility of this animal modelling approach for exploring neurobiological mechanisms that generate or modulate ASSRs.",
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AU - Chambers, R.

AU - Krishnan, Giri P.

AU - O'Donnell, Brian

AU - Berg, Sarah

AU - Morzorati, Sandra

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N2 - Auditory steady-state auditory responses (ASSRs), in which the evoked potential entrains to stimulus frequency and phase, are reduced in magnitude in patients with schizophrenia, particularly at 40 Hz. While the neural mechanisms responsible for ASSR generation and its perturbation in schizophrenia are unknown, it has been hypothesized that the GABAA receptor subtype may have an important role. Using an established rat model of schizophrenia, the neonatal ventral hippocampal lesion (NVHL) model, 40-Hz ASSRs were elicited from NVHL and sham rats to determine if NVHL rats show deficits comparable to schizophrenia, and to examine the role of GABAA receptors in ASSR generation. ASSR parameters were found to be stable across time in both NVHL and sham rats. Manipulation of the GABAA receptor by muscimol, a GABAA agonist, yielded a strong lesiondrug interaction, with ASSR magnitude and synchronization decreased in NVHL and increased in sham rats. The lesionmuscimol interaction was blocked by a GABAA receptor antagonist when given prior to muscimol administration, confirming the observed interaction was GABAA mediated. Together, these data suggest an alteration involving GABAA receptor function, and hence inhibitory transmission, in the neuronal networks responsible for ASSR generation in NVHL rats. These findings are consistent with prior evidence for alterations in GABA neurotransmitter systems in the NVHL model and suggest the utility of this animal modelling approach for exploring neurobiological mechanisms that generate or modulate ASSRs.

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