Sex differences in (+)-amphetamine- and (+)-methamphetamine-induced behavioral response in male and female Sprague–Dawley rats

Abstract

(+)-Methamphetamine (METH) and (+)-amphetamine (AMP) are structurally similar drugs that are reported to induce similar pharmacological effects in rats of the same sex. Because pharmacokinetic data suggest female rats should be more affected than males, the current studies sought to test the hypothesis that the behavioral and temporal actions of METH and AMP should be greater in female Sprague-Dawley rats than in males. Using a dosing regimen designed to reduce the possibility of tolerance and sensitization, rats were administered 1.0 and 3.0 mg/kg intravenous drug doses. Distance traveled, rearing events and focal stereotypies (e.g., head weaving, sniffing) were measured. Female rats traveled significantly greater distances and displayed a greater number of rearing events than males after both doses. Analysis of stereotypy ratings after 3.0 mg/kg revealed that focal stereotypies were more pronounced and lasted longer in females. The second study compared the potencies of METH and AMP in inducing locomotor activity and focal stereotypies in each sex. No differences in potency were found when METH and AMP effects were compared within males or females. In summary, these studies showed female rats displayed greater and longer-lasting locomotor activity and more stereotypic behaviors, supporting earlier evidence of significant sexual dimorphism in pharmacokinetics.

Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

“…As mentioned before, females were shown to be more sensitive to the effect of AMP treatment than males (Camp and Robinson, 1988;Forgie and Stewart, 1993;Bisagno et al, 2003;Páleníček et al, 2005;Milesi-Halle et al, 2007). Moreover, it seems that male rats were able to recall the location of the platform more effectively than females, as they displayed faster learning.…”

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

“…Among preweanling and adolescent rats, the sex variable did not influence cocaine-induced locomotor activity (see also Snyder et al 1998; Kozanian et al 2012); however, adult female rats injected with 10 or 20 mg/kg cocaine did show more locomotor activity than similarly-treated adult males. This is not a novel finding since many psychostimulants (e.g., cocaine, amphetamine, and methamphetamine) induce an excess of locomotor activity in adult female rats and mice (Schindler and Carmona 2002; Festa et al 2004; Milesi-Hallé et al 2005, 2007). Importantly, changes in the number of high affinity D2 receptors cannot account for sex-related differences in cocaine sensitivity, because the heightened locomotor response shown by female rats treated with 20 mg/kg cocaine was not matched by an increase in D2 High receptors.…”

Treatment with a Monoclonal Antibody against Methamphetamine and Amphetamine Reduces Maternal and Fetal Rat Brain Concentrations in Late Pregnancy

“…METH dose can cause maternal and fetal death (White et al, 2011). Although not directly toxic, a 1 mg/kg dose produces significant METH-induced behaviors in female rats (Milesi-Hallé et al, 2007). Changes in maternal behaviors resulting from chronic treatment with METH can result in significant changes in the dam's ability to nurse, groom, and dmd.aspetjournals.org build nests for their pups (Slamberová et al, 2006).…”