Objective: The anxiety profile in the stimulant-sensitized animals is not clear. Thus, this study was conducted to elucidate the effects of acute and chronic administration of methamphetamine (METH) on the anxiety profile. The aim of this study was to examine whether METH-sensitized rats would show an increase in the expression of anxiogenic-like behaviors and to determine whether a low dose of METH elicits behavioral sensitization. Methods:Rats were repeatedly given METH (2 mg/kg, s.c., once a day for 14 days), and the immediate and delayed effects of METH on the anxiety profile was compared considering 30 minutes (min) and 120 min after injections in METH-sensitized, withdrawn and intact rats using the elevated plus-maze (EPM), also, to re-challenge with a low dose of METH (0.5 mg/kg) in withdrawn groups . Results:Results have shown that METH-sensitized rats exhibited an increase in the open arm time and entries 120 min after injection compared to the control group. We found a reduction in the time spent in open arms for the immediate effects of METH (30 min after injection) in METH-sensitized rats as compared to the control group. In withdrawn rats, METH/METH groups exhibited an increase in the open arm time and entries than METH/Sal and Sal/METH groups. Conclusion:It was found that unlike delayed effects, an immediate effect of METH exhibited anxiogenic-like behaviors in METH-sensitized rats using the EPM. Also, results indicated that a low dose of METH is a potent stimulus for reinstatement of methamphetamine behavioral sensitization in a long withdrawn period.

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