Sex differences in the acute locomotor response to methamphetamine in BALB/c mice

Abstract

Women use methamphetamine more frequently than men and are more vulnerable to its negative psychological effects. Rodent models have been an essential tool for evaluating the sex-dependent effects of psychostimulants; however, evidence of sex differences in the behavioral responses to methamphetamine in mice is lacking. In the present study, we investigated acute methamphetamine-induced (1 mg/kg and 4 mg/kg) locomotor activation in female and male BALB/c mice. We also evaluated whether basal locomotor activity was associated with the methamphetamine-induced locomotor response. The results indicated that female BALB/c mice displayed enhanced methamphetamine-induced locomotor activity compared to males, while basal locomotor activity was positively correlated with methamphetamine-induced activity in males, but not females. This study is the first to show sex-dependent locomotor effects of methamphetamine in BALB/c mice. Our observations emphasize the importance of considering sex when assessing behavioral responses to methamphetamine.

Gender differences in the behavioral and subjective effects of methamphetamine in healthy humans

“…Overall, we find that MA administration produces faster reaction times in women, but does not significantly affect behavior in men. This is in line with preclinical research suggesting that female rodents are more sensitive to the psychomotor-activating effects of MA than males (Milesi-Hallé et al 2007; Ohia-Nwoko et al 2017; Schindler et al 2002). Moreover, we find that MA increased ratings of vigor (POMS) and reduced ratings of sedation (ARCI—PCAG) to a greater extent in women than in men.…”

“…Variations in responses to acute doses of stimulant drugs may also be detected with objective, behavioral measures. Female rodents are more sensitive to the psychomotor effects of cocaine, amphetamine, and MA (Becker 1999; Hu and Becker 2003; Milesi-Hallé et al 2007; Ohia-Nwoko et al 2017; Schindler et al 2002). While female rodents are also more sensitive to the reinforcing effects of cocaine (Lynch and Carroll 1999, 2000), this sex difference appears to be less evident with amphetamine and MA (Mattei and Carlini 1996; Schindler et al 2002; Stöhr et al 1998).…”

Antagonism of Neurotensin Receptors in the Ventral Tegmental Area Decreases Methamphetamine Self-Administration and Methamphetamine Seeking in Mice

“…Sex differences have previously been reported in the context of dopamine and other neuropeptides such as oxytocin ( Cox et al, 2013 ); however, this has not been explored regarding neurotensin. Indeed, a recent report suggests that METH-induced locomotor activity and stereotypy behavior may be enhanced in female compared with male rodents ( Milesi-Hallé et al, 2007 ; Ohia-Kwoko et al, 2017 ). Further research will be needed to address sex differences in the acquisition of METH self-administration and METH-seeking behavior ( Roth and Carroll, 2004 ; Ruda-Kucerova et al, 2015 ) and the possible implications of a role for neurotensin in METH self-administration.…”

Sex Differences in Context-Driven Reinstatement of Methamphetamine Seeking is Associated with Distinct Neuroadaptations in the Dentate Gyrus

“…Studies in rats show that males experience more severe withdrawal effects than females after chronic cocaine intake [11], suggesting that elevated drug use in females may be due to their greater sensitivity to rewarding effects of the drug and to their resilience to the negative affect associated with withdrawal. Alternatively, higher active lever responses in females may be due to increased sensitivity to methamphetamine-induced psychomotor effects, since females exhibit greater locomotion and more stereotypy in response to methamphetamine than males [12,37,38]. This possibility is diminished because inactive lever responses did not differ between males and females, suggesting that active lever responses in females is not a result of hyperactivity.…”