Abstract
In this study, we investigated the antipsychotic-like effect of methanolic extract of Mitragyna speciosa leaf (MMS) using in vivo and ex vivo studies. In vivo studies comprised of apomorphine-induced climbing behavior, haloperidol-induced catalepsy, and ketamine-induced social withdrawal tests in mice whereas the ex vivo study was conducted utilizing isolated rat vas deferens preparation. Acute oral administration of MMS (50–500 mg/kg) showed an inverted bell-shaped dose-response in apomorphine-induced cage climbing behavior in mice. The effective inhibitory doses of MMS (75 and 100 mg/kg, p.o.) obtained from the apomorphine study was further tested on haloperidol (subcataleptic dose; 0.1 mg/kg, i.p.)-induced catalepsy in the mouse bar test. MMS (75 and 100 mg/kg, p.o.) significantly potentiated the haloperidol-induced catalepsy in mice. Interestingly, MMS at the same effective doses (75 and 100 mg/kg, p.o.) significantly facilitated the social interaction in ketamine-induced social withdrawal mice. Furthermore, MMS inhibited the dopamine-induced contractile response dose-dependently in the isolated rat vas deferens preparations. In conclusion, this investigation provides first evidence that MMS exhibits antipsychotic-like activity with potential to alleviate positive as well as negative symptoms of psychosis in mice. This study also suggests the antidopaminergic activity of MMS that could be responsible for alleviating positive symptoms of psychosis.
Highlights
Psychosis is a devastating mental illness with a high economic burden for many countries
Psychosis animal models are developed based on the neurochemical theory of schizophrenia, primarily involving neurotransmitters such as dopamine and glutamate and it has been used to screen new chemical entities (NCEs) for potential antipsychotic-like effect (Lipska and Weinberger, 2000)
This study demonstrated that the acute oral treatment of methanolic extract of Mitragyna speciosa leaf (MMS) (50, 75, 100, 125, 250, and 500 mg/kg) showed an inverted bell-shaped dose-response relationship in the mouse cage climbing behavior
Summary
Psychosis is a devastating mental illness with a high economic burden for many countries. Available antipsychotics are mainly classified into two categories: typical antipsychotics (e.g., chlorpromazine, haloperidol etc.) and atypical antipsychotics (e.g., clozapine, risperidone etc.) The former class of drugs are effective to treat only the positive symptoms such as delusion, Mitragyna speciosa Exhibits Antipsychotic-Like Effect hallucination, and stereotypy behavior by blocking dopamine D2 receptors of the mesolimbic pathway in the brain whereas atypical antipsychotics are able to treat both positive as well as negative symptoms such as withdrawal from social contacts, anhedonia, and flattening of emotional responses by blocking D2, 5HT2A, and adrenergic (α2) receptors (Horacek et al, 2006). A search for an alternative antipsychotics to effectively treat both positive and negative symptoms with lesser or no adverse effects is a continuous process in the research world
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