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Sex differences in the discriminative stimulus effects of m-chlorophenylpiperazine and ethanol withdrawal
M E Jung1, C J Wallis, M B Gatch
1Department of Pharmacology and Substance Abuse Institute of North Texas, University of North Texas Health Science Center at Fort Worth, 76107-2699, USA. mjung@hsc.unt.edu
Rationale:
The serotonergic system plays a role in regulation of anxiety and ethanol withdrawal (EW). Nevertheless, few studies have assessed sex differences in serotonergic effects on EW.
Objectives:
This study examined sex differences in the anxiogenic stimuli induced by a serotonin (5-HT)(1b,2) agonist, meta-chlorophenylpiperazine (mCPP), prior to ethanol and during EW.
Methods:
Gonadectomized or sham-operated adult male and female rats and 17beta-estradiol (2.5 mg, 21-day release, s.c.) -replaced ovariectomized (OVX) rats were trained to discriminate mCPP (1.2 mg/kg, i.p.) from saline in a two-lever choice task for food. Latency to the first lever press and mCPP lever selection were measured following mCPP (0-1.2 mg/kg). Rats then received chronic ethanol-containing liquid diet (6.5%) for 10 days and were tested for mCPP lever selection 12 h and 36 h after removal of ethanol.
Results:
Fewer sham female and beta-estradiol-replaced OVX rats selected the mCPP lever than male or OVX rats, and showed an increased initiation latency after mCPP injection. During EW (12 h and 36 h), fewer sham female and beta-estradiol-replaced OVX rats responded on the mCPP-lever after saline injection as well as after mCPP challenge than male or OVX rats. Castration did not alter any response of male rats to mCPP.
Conclusions:
(1) mCPP discrimination is a useful measure of EW in male and female rats; and (2) sham female and beta-estradiol-replaced OVX rats are less sensitive to the discriminative stimulus prior to and during EW, but more sensitive to impaired behavioral initiation induced by mCPP than male or OVX rats.