Sex differences in the pentylenetetrazol-like stimulus induced by ethanol withdrawal

This study investigated sex differences in responding to the pentylenetetra zol (PTZ, a gamma-aminobutyric acid A antagonist) discriminative stimulus a nd to substitution to PTZ during ethanol withdrawal. The PTZ stimulus has s erved as an anxiogenic stimulus in numerous studies. Adult male and female rats were trained to discriminate PTZ (16 mg/kg i.p.) from saline in a two- lever food-reinforced task. They were then gonadectomized or sham-operated. Ovariectomized (OVX) rats were also tested during 17 beta-estradiol (2.5 m g, 21 days release, s.c.) replacement. The PTZ dose response (0-16 mg/kg i. p.) was tested in all groups. In general, fewer females than males responde d to PTZ. Diazepam (DZP; 0-10 mg/kg i.p.) injected before PTZ (16 mg/kg) de creased the number of rats selecting the PTZ lever. This effect was greater in sham female and estradiol-replaced-OVX rats than in male or OVX rats. R ats then received chronic ethanol diet (6.5%) for 10 days. During ethanol w ithdrawal (12 h after termination of the ethanol diet), they were tested fo r PTZ lever selection. PTZ lever selection differed between groups: sham or castrated male rats. OVX. sham female or estradiol-replaced-OVX rats. In s ham female rats, estradiol concentrations showed a cyclic pattern with an e stradiol surge that did not influence their PTZ discrimination performance. After i.p. injection of ethanol (2 g/kg), blood ethanol concentrations wer e not different in male and female rats. These findings suggest that 1) fem ale rats are less sensitive to the anxiogenic effects of PTZ; 2) female rat s are less sensitive to the anxiogenic effects of ethanol withdrawal; and 3 ) estrogen plays some role in mediation of these sex differences.