Sex differences in the discriminative stimulus effects of m-chlorophenylpiperazine and ethanol withdrawal.
BACKGROUND
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.


OBJECTIVE
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.
Jung
M E
ME
Department 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
Wallis
C J
CJ
Gatch
M B
MB
Lal
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D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D005260:Female; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans / Q000601:surgery; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012727:Sex Characteristics; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology*
D002492:Central Nervous System Depressants; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D000431:Ethanol; C015068:1-(3-chlorophenyl)piperazine