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Sex-specific effects of prenatal methamphetamine exposure on activity and blood pressure in aged offspring
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DOI：10.3389/fnbeh.2026.1772937.png)
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Abstract
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IntroductionMethamphetamine use during pregnancy is a global health issue; and there is limited knowledge on the cardiovascular and behavioral effects of prenatal methamphetamine exposure in adults. This study investigated how prenatal methamphetamine exposure in rats; via maternal intravenous self-administration; affected methamphetamine sensitivity and cardiovascular function in aged offspring compared to controls.MethodsThe aged offspring were generated from dams either self-administering methamphetamine daily under extended-access conditions before and throughout pregnancy; or their respective sham control dams. Spontaneous and methamphetamine-induced locomotor activity was assessed in male and female offspring of both exposure groups after a range of methamphetamine doses at age 15–17 months. Cardiovascular function was assessed in male and female offspring aged 18–20 months of both groups.ResultsBaseline blood pressure and angiotensin II (AngII)-induced hypertension were determined non-invasively via tail cuff measurements. Methamphetamine dose-dependently increased locomotor activity compared to baseline activity in both sexes and both exposure groups. In both sexes; AngII did not increase diastolic or systolic blood pressure in methamphetamine-exposed offspring; yet induced hypertension in controls. Methamphetamine administration induced dose-dependent hyperactivity in both exposure groups; with methamphetamine-exposed offspring showing resistance to stereotypic effects and thus increased activity at 3.2 mg/kg compared to controls. Notably; methamphetamine-exposed female offspring had a tendency to hypertension at baseline; driven by higher diastolic blood pressure; and showed reduced hyperactivity compared to controls at 1.0 mg/kg. Males did not exhibit these changes.ConclusionThese findings suggest that aged female offspring are particularly sensitive to the impacts of prenatal methamphetamine exposure on blood pressure and methamphetamine sensitivity.
Keywords:
locomotor activity
methamphetamine
prenatal exposure
blood pressure
long-term effects
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