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Evaluation of anti-manic activity of pregabalin in a mouse model of methylphenidate-induced mania

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MALIKOWSKA N., GRZYWA A., ŚLADOWSKA J., SAŁAT K., LIBROWSKI T., GDULA-ARGASIŃSKA J.

Medicina Internacia Revuo

2017

vol. 28

issue 108

196-201

Mania is a psychiatric disorder which may occur alternately with depression as a bipolar disorder, or much less often as an individual disease. It might be accompanied by other disorders, i.e. schizophrenia, dementia or withdrawal syndrome. Only a few effective drugs are used for the treatment of mania. Patients suffering from bipolar disorder are treated with mood-stabilizing drugs, administered during the course of the disease, and drugs that are implemented when mania or depression episodes occur. Some studies report effectiveness of anticonvulsant drugs in the cessation of mania, thus in our study we assessed the effectiveness of pregabalin in a mouse model of mania induced by administration of metylphenidate (5 mg/kg; s.c). Pregabalin was tested in the forced swim test (75 mg/kg, 100 mg/kg; i.p.) and the elevated plus maze test (75 mg/kg; i.p.) to assess its antidepressant-like and anxiolytic-like properties, respectively. In the elevated plus maze in MPH-treated mice pregabalin significantly reduced time spent in open arms (p<0.001 vs. MPH-treated control). In the forced swim test MPH compared to vehicle significantly (p<0.001) reduced duration of immobility. In MPH-treated mice pregabalin partially reversed this effect of MPH. This effect was significant only for the dose of 75 mg/ kg (p<0.05). In the rotarod test neither MPH, nor its combination with pregabalin (75 mg/kg; 100 mg/kg) influenced motor coordination of mice at any speed tested. To conclude our study revealed that pregabalin might reverse manic-like action of MPH related to hyperlocomotion, which may indicate for its possible effectiveness in mania episodes.

PHARMACOLOGICAL ACTIVITY OF NOVEL GABA RE-UPTAKE INHIBITORS IN MICE

84%

PODKOWA A., GRZYWA A., LECHOCKA A., SZLONZAK A., KOWALCZYK P., KULIG K., FILIPEK B., SAŁAT K.

Medicina Internacia Revuo

2014

vol. 26

issue 102

32- 41

Γ-aminobutyric acid (GABA) is a widely distributed neurotransmitter in the mammalian central nerv-ous system. The GABAergic neurotransmission is involved in numerous processes, including neuronal excitability and mood disorders. GABA is removed from the synaptic cleft by specific proteins called plasma membrane GABA transporters. In the present work we focus on antinociceptive and antidepres-sant-like properties of four new GABA re-uptake inhibitors. These compounds are N-benzylamide derivatives of GABA. We also investigate their impact on animal’ locomotor activity and motor coordina-tion. All the examined compounds present analgesic activity in the hot plate test. Most of them also demonstrate antidepressant-like properties in the forced swim test in mice. Similarly to tiagabine, the test compounds significantly affect locomotor activity and some of them cause motor coordination impair-ments. The obtained results suggest that compounds targeting at GABA transporters may exert analgesic and antidepressant-like properties.

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2 Medicina Internacia Revuo

1 2017

1 2014

2 GRZYWA A.

2 SAŁAT K.

1 FILIPEK B.

1 GDULA-ARGASIŃSKA J.

1 KOWALCZYK P.

1 KULIG K.

1 LECHOCKA A.

1 LIBROWSKI T.

1 MALIKOWSKA N.

1 PODKOWA A.

1 SZLONZAK A.

1 ŚLADOWSKA J.

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Evaluation of anti-manic activity of pregabalin in a mouse model of methylphenidate-induced mania

PHARMACOLOGICAL ACTIVITY OF NOVEL GABA RE-UPTAKE INHIBITORS IN MICE