Antipsychotic-like effect of trimetazidine in a rodent model

Objectives: Schizophrenia is a psychiatric disorder, which is thought to have close relationship with hyperdopaminergic activity. Trimetazidine an anti-ischemic drug, has been used in cardiology practice due to its protective effects particularly against myocardial ischemia and reperfusion injury. Trimetazidine is thought to carry out its effects via supporting cellular homeostasis during ischemia-reperfusion injury.

Methods: Apomorphine-Induced Stereotypic Behavior Test: Mesolimbic and nigrostriatal dopaminergic pathways play crucial roles in the mediation of locomotor activity and stereotyped behavior. Apomorphine induced stereotypy is due to the stimulation of dopamine receptors and has been used as a convenient method for in vivo screening of dopamine agonists or antagonists and assessment of dopaminergic activity. Brieşy, four groups of rat (n=7) were administered TMZ (10 and 20 mg/kg, i.p.), chlorpromazine (1 mg/kg, i.p.), and isotonic saline (1 mL/kg, i.p.). One hour later, apomorphine (2 mg/kg, s.c.) was administered to each rat. First, rats were placed into the cylindrical metal cages (18 × 19 cm) containing vertical (1 cm apart) and horizontal (4.5 cm apart) metal bars (2 mm) with upper lid for 10 minutes for orientation period. After apomorphine administration, the rats were immediately placed back into the metal cages and observed for stereotypic behavior. Signs of stereotypy, which include mainly sniffing and gnawing, were observed and scored as follows: absence of stereotypy (0), occasional sniffing (1), occasional sniffing with occasional gnawing (2), frequent gnawing (3), intense continuous gnawing (4), and intense gnawing and staying on the same spot (5). The stereotypic behavior was rated after each minute, and mean of 15 min period was calculated and recorded.

Results: The inhibitory effect of TMZ on rearing behavior was dose dependent, being more evident at a higher dose (20 mg/kg). Post-hoc Bonferonni test demonstrated a highly significant decrease in stereotypy scores in both doses of TMZ and chlorpromazine compared to saline group The decrease was significantly greater with 20 mg/kg of TMZ compared to 10 mg/kg

Conclusion: This study demonstrates the beneficial effects of TMZ on rearing behavior and stereotypy, which are accepted to be indicators of anti-psychotic effect.