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Health behaviour

Does meth break male and female prefrontal neurons the same way?

Chen L, Kreko-Pierce T, Cassoday SL, et al. · Frontiers in pharmacology · 2025

Open access · cc by · source: Europe PMC

In 94 F344 rats, males and females self-administered similar meth (≈28–29 mg/kg over 21 days) and kept seeking at 30 days, but VGCC calcium spikes fell in males and rose in females after short withdrawal.

Study at a glance

Design
Animal / in-vitro — F344 rat methamphetamine self-administration with yoked saline, then whole-cell patch of mPFC pyramids after 2–5 d or ≥30 d withdrawal
N
N=94 · 94 rats (49 female, 45 male); short-term withdrawal 29F/28M; long-term 20F/17M, with overlapping ephys cells
Population
4–5-month-old male and female F344 rats after 21-day i.v. meth self-administration
Outcome
Drug taking/seeking, mPFC pyramidal excitability, and VGCC calcium-spike area/duration by sex and withdrawal time

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Key findings

Intake did not differ by sex (27.8±2.3 vs 29.1±2.1 mg/kg). Both sexes showed persistent 30-day seeking. After short withdrawal, male calcium-spike area/duration decreased while female spikes increased (sex×meth p≤0.003).

Methodology

Ran 21-day meth self-administration vs saline-yoked controls in male and female rats, tested cue-induced seeking during long withdrawal, and whole-cell patched mPFC pyramids after 2–5 or ≥30 days for firing and VGCC calcium spikes.

Limitations

Rat operant meth is not a clinical trial of gender-specific treatment; overlapping cell counts are small, and mPFC slice physiology does not measure human cognition.

How this study connects

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