open access

https://doi.org/10.11501/3151343

https://hdl.handle.net/2115/51584

The Role of Gamma-aminobutyric Acid (GABA) : Benzodiazepine Neurotransmission in the Animal Modei of Methamphetamine-induced Psychosis

日本語

GABA

1999-03-25

Hokkaido University

Repeated administration of amphetamine or methamphetamine (MA) results in an augmentation of its locomotor activating effects, a phenomenon known as behavioral sensitization. In humans, the chronic use of the drug elicits a progressive augmentation in paranoid symptoms that closely resemble schizophrenia. Behavioral sensitization has some common properties with other forms of neural plasticity such as kindling, learning and long-term potentiation (LTP). The present study examined whether behavioral sensitization would be blocked by GABA-benzodiazepine agonists, known to inhibit kindling, learning as well as LTP. Rats (Male Wistar-King rats) treated with MA (1mg/kg, s.c.) for 1O days displayed significantly enhanced motor activity when tested with MA (1mg/kg) after a 7-8 day withdrawal, indicating the acquisition of behavioral sensitization. Pretreatment with clonazepam (CZP) (0.5 and 2.0mg/kg), a GABA-benzodiazepine agonists, prior to MA administration prevented the acquisition of the phenomenon. In contrast, pretreatment with flumazenil (Flu) (1Omg/kg), a GABA-benzodiazepine antagonist, prior to MA administration has no influence on the acquisition of sensitization. However, pretreatment with Flu prior to CZP administration reversed the inhibitory effect of CZP. CZP showed no effect on the expression of sensitization in the sensitized rats when given prior to the MA readminisiration. These results suggest that stimulation of GABA-benzodiazepine receptors plays a role in the acquisition but not in the expression of behavioral sensitization.

1999-03-25

甲第4661号

博士(医学)

博士論文

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