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

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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.

Source

Methamphetamine self-administration causes neuronal dysfunction in rat medial prefrontal cortex in a sex-specific and withdrawal time-dependent manner

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

doi.org/10.3389/fphar.2025.1527795Read the full paper ↗6 citationscc by

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

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

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.

What they found

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).

The limits

What it doesn't show

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.

Key terms

Meth-SA
Intravenous methamphetamine self-administration in operant chambers.
mPFC
Medial prefrontal cortex; source of recorded glutamatergic pyramids.
Yoked saline
Control rats receiving saline infusions matched to a meth partner’s timing.
VGCC
Voltage-gated calcium channel; source of measured calcium plateau spikes.
Withdrawal
Short (2–5 d) vs long (≥30 d) abstinence after 21 days of Meth-SA.
Drug-seeking
Active nose-pokes for meth-paired cues without drug delivery.

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Animal N was about:

Common questions

How many rats?

94 (49 female, 45 male).

Did intake differ by sex?

No—about 28 vs 29 mg/kg over 21 days.

Did seeking persist?

Yes, in both sexes across 30-day withdrawal.

How did VGCCs differ?

Males decreased, females increased calcium spikes after short withdrawal.

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