Effects of mood stabilizers on marble-burying behavior in mice: Involvement of GABAergic system

Nobuaki Egashira, Moe Abe, Atsunori Shirakawa, Tomiko Niki, Kenichi Mishima, Katsunori Iwasaki, Ryozo Oishi, Michihiro Fujiwara

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Rationale: Obsessive-compulsive disorder (OCD) is characterized by recurrent unwanted thoughts (obsessions), usually accompanied by repetitive behaviors (compulsions) intended to alleviate anxiety. Marble-burying behavior is a pharmacological model for study of OCD. Objectives: In the present study, we examined the effects of mood stabilizers on marble-burying behavior in mice, as well as the role of GABA receptors in this behavior. Methods: The effects of treatment with valproate, carbamazepine, lithium carbonate, lamotrigine, muscimol and baclofen on marble-burying behavior in mice were evaluated. Results: Valproate (10, 30 and 100 mg/kg, i.p.) and carbamazepine (30 and 100 mg/kg, p.o.) significantly reduced marble-burying behavior without affecting total locomotor activity in ICR mice. Lamotrigine (30 mg/kg, i.p.) also significantly reduced marble-burying behavior in ddY mice. On the other hand, lithium carbonate (10, 30 and 100 mg/kg, i.p.) reduced total locomotor activity without affecting marble-burying behavior in ddY mice. The selective GABA A receptor agonist muscimol (1 mg/kg) significantly reduced marble-burying behavior without affecting total locomotor activity, whereas the selective GABAB receptor agonist baclofen (3 mg/kg) reduced total locomotor activity without affecting marble-burying behavior. Moreover, the selective GABAA receptor antagonist bicuculline (3 mg/kg) significantly counteracted the decrease in marble-burying induced by the administration of muscimol (1 mg/kg) and valproate (100 mg/kg). Conclusions: These results suggest that GABAergic mechanism is involved in marble-burying behavior, and that valproate, carbamazepine and lamotrigine reduce marble-burying behavior. Moreover, valproate reduces marble-burying behavior via a GABAA receptor-dependent mechanism.

Original languageEnglish
Pages (from-to)295-305
Number of pages11
JournalPsychopharmacology
Volume226
Issue number2
DOIs
Publication statusPublished - Mar 1 2013

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Calcium Carbonate
Valproic Acid
Locomotion
Muscimol
Carbamazepine
Lithium Carbonate
Obsessive-Compulsive Disorder
GABA-B Receptors
GABA-A Receptor Agonists
GABA-A Receptor Antagonists
Obsessive Behavior
Inbred ICR Mouse
Baclofen
GABA Receptors
Bicuculline
GABA-A Receptors
Anxiety
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Effects of mood stabilizers on marble-burying behavior in mice : Involvement of GABAergic system. / Egashira, Nobuaki; Abe, Moe; Shirakawa, Atsunori; Niki, Tomiko; Mishima, Kenichi; Iwasaki, Katsunori; Oishi, Ryozo; Fujiwara, Michihiro.

In: Psychopharmacology, Vol. 226, No. 2, 01.03.2013, p. 295-305.

Research output: Contribution to journalArticle

Egashira, N, Abe, M, Shirakawa, A, Niki, T, Mishima, K, Iwasaki, K, Oishi, R & Fujiwara, M 2013, 'Effects of mood stabilizers on marble-burying behavior in mice: Involvement of GABAergic system', Psychopharmacology, vol. 226, no. 2, pp. 295-305. https://doi.org/10.1007/s00213-012-2904-9
Egashira, Nobuaki ; Abe, Moe ; Shirakawa, Atsunori ; Niki, Tomiko ; Mishima, Kenichi ; Iwasaki, Katsunori ; Oishi, Ryozo ; Fujiwara, Michihiro. / Effects of mood stabilizers on marble-burying behavior in mice : Involvement of GABAergic system. In: Psychopharmacology. 2013 ; Vol. 226, No. 2. pp. 295-305.
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abstract = "Rationale: Obsessive-compulsive disorder (OCD) is characterized by recurrent unwanted thoughts (obsessions), usually accompanied by repetitive behaviors (compulsions) intended to alleviate anxiety. Marble-burying behavior is a pharmacological model for study of OCD. Objectives: In the present study, we examined the effects of mood stabilizers on marble-burying behavior in mice, as well as the role of GABA receptors in this behavior. Methods: The effects of treatment with valproate, carbamazepine, lithium carbonate, lamotrigine, muscimol and baclofen on marble-burying behavior in mice were evaluated. Results: Valproate (10, 30 and 100 mg/kg, i.p.) and carbamazepine (30 and 100 mg/kg, p.o.) significantly reduced marble-burying behavior without affecting total locomotor activity in ICR mice. Lamotrigine (30 mg/kg, i.p.) also significantly reduced marble-burying behavior in ddY mice. On the other hand, lithium carbonate (10, 30 and 100 mg/kg, i.p.) reduced total locomotor activity without affecting marble-burying behavior in ddY mice. The selective GABA A receptor agonist muscimol (1 mg/kg) significantly reduced marble-burying behavior without affecting total locomotor activity, whereas the selective GABAB receptor agonist baclofen (3 mg/kg) reduced total locomotor activity without affecting marble-burying behavior. Moreover, the selective GABAA receptor antagonist bicuculline (3 mg/kg) significantly counteracted the decrease in marble-burying induced by the administration of muscimol (1 mg/kg) and valproate (100 mg/kg). Conclusions: These results suggest that GABAergic mechanism is involved in marble-burying behavior, and that valproate, carbamazepine and lamotrigine reduce marble-burying behavior. Moreover, valproate reduces marble-burying behavior via a GABAA receptor-dependent mechanism.",
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AU - Niki, Tomiko

AU - Mishima, Kenichi

AU - Iwasaki, Katsunori

AU - Oishi, Ryozo

AU - Fujiwara, Michihiro

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N2 - Rationale: Obsessive-compulsive disorder (OCD) is characterized by recurrent unwanted thoughts (obsessions), usually accompanied by repetitive behaviors (compulsions) intended to alleviate anxiety. Marble-burying behavior is a pharmacological model for study of OCD. Objectives: In the present study, we examined the effects of mood stabilizers on marble-burying behavior in mice, as well as the role of GABA receptors in this behavior. Methods: The effects of treatment with valproate, carbamazepine, lithium carbonate, lamotrigine, muscimol and baclofen on marble-burying behavior in mice were evaluated. Results: Valproate (10, 30 and 100 mg/kg, i.p.) and carbamazepine (30 and 100 mg/kg, p.o.) significantly reduced marble-burying behavior without affecting total locomotor activity in ICR mice. Lamotrigine (30 mg/kg, i.p.) also significantly reduced marble-burying behavior in ddY mice. On the other hand, lithium carbonate (10, 30 and 100 mg/kg, i.p.) reduced total locomotor activity without affecting marble-burying behavior in ddY mice. The selective GABA A receptor agonist muscimol (1 mg/kg) significantly reduced marble-burying behavior without affecting total locomotor activity, whereas the selective GABAB receptor agonist baclofen (3 mg/kg) reduced total locomotor activity without affecting marble-burying behavior. Moreover, the selective GABAA receptor antagonist bicuculline (3 mg/kg) significantly counteracted the decrease in marble-burying induced by the administration of muscimol (1 mg/kg) and valproate (100 mg/kg). Conclusions: These results suggest that GABAergic mechanism is involved in marble-burying behavior, and that valproate, carbamazepine and lamotrigine reduce marble-burying behavior. Moreover, valproate reduces marble-burying behavior via a GABAA receptor-dependent mechanism.

AB - Rationale: Obsessive-compulsive disorder (OCD) is characterized by recurrent unwanted thoughts (obsessions), usually accompanied by repetitive behaviors (compulsions) intended to alleviate anxiety. Marble-burying behavior is a pharmacological model for study of OCD. Objectives: In the present study, we examined the effects of mood stabilizers on marble-burying behavior in mice, as well as the role of GABA receptors in this behavior. Methods: The effects of treatment with valproate, carbamazepine, lithium carbonate, lamotrigine, muscimol and baclofen on marble-burying behavior in mice were evaluated. Results: Valproate (10, 30 and 100 mg/kg, i.p.) and carbamazepine (30 and 100 mg/kg, p.o.) significantly reduced marble-burying behavior without affecting total locomotor activity in ICR mice. Lamotrigine (30 mg/kg, i.p.) also significantly reduced marble-burying behavior in ddY mice. On the other hand, lithium carbonate (10, 30 and 100 mg/kg, i.p.) reduced total locomotor activity without affecting marble-burying behavior in ddY mice. The selective GABA A receptor agonist muscimol (1 mg/kg) significantly reduced marble-burying behavior without affecting total locomotor activity, whereas the selective GABAB receptor agonist baclofen (3 mg/kg) reduced total locomotor activity without affecting marble-burying behavior. Moreover, the selective GABAA receptor antagonist bicuculline (3 mg/kg) significantly counteracted the decrease in marble-burying induced by the administration of muscimol (1 mg/kg) and valproate (100 mg/kg). Conclusions: These results suggest that GABAergic mechanism is involved in marble-burying behavior, and that valproate, carbamazepine and lamotrigine reduce marble-burying behavior. Moreover, valproate reduces marble-burying behavior via a GABAA receptor-dependent mechanism.

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