Abstract
There are sex differences in the symptomatology of schizophrenia, and in the response to antipsychotic treatments. One hallmark symptom of schizophrenia is a deficit in selective attention. Selective attention can be measured using a latent inhibition (LI) paradigm in humans; LI can be measured in rodents, and is used as an animal model of the selective attention deficits observed in schizophrenia. In the current experiments LI was used to clarify whether selective attention differs between male rats and ovariectomized (OVX) female rats receiving different estradiol (E2) replacement regimens. An additional aim was to determine whether haloperidol’s (HAL) facilitation of LI is enhanced by E2. Males and OVX female rats were trained in a conditioned emotional response LI paradigm. Females received no E2 replacement, a chronic low dose of E2 via silastic capsule, or a high phasic dose of E2 via silastic capsule accompanied by E2 (10 µg/kg subcutaneous (SC)) injections every 4th day. Actual plasma levels of E2 were determined using an enzyme linked immunosorbent assay. Rats were also administered a vehicle treatment, a 0.05 mg/kg, or a 0.1 mg/kg IP injection of HAL. Males and OVX females that did not receive E2 replacement both exhibited LI, but LI was not observed in the low and high E2 replacement groups. HAL restored LI at a lower dose in the females receiving high E2 replacement compared to females receiving low E2 replacement, indicating that E2 replacement facilitates HAL in restoring LI.
Highlights
There are sex differences in schizophrenia, in the positive symptoms of this disorder, with women developing schizophrenia later in life and exhibiting less severe symptomatology than males (Häfner et al, 1992; Häfner, 2003; Kulkarni et al, 2008)
There is some evidence that estrogen is linked to greater efficacy of antipsychotic treatments, as positive symptoms of schizophrenia are further reduced when antipsychotics are co-administered with estrogen than when administered alone (Akhondzadeh et al, 2003; Seeman, 2004)
Females are more responsive to antipsychotics than males (Seeman, 2004), and these results suggest that estrogens contribute to this sex difference differing responses to HAL in males and females in an latent inhibition (LI) paradigm
Summary
There are sex differences in schizophrenia, in the positive symptoms of this disorder, with women developing schizophrenia later in life and exhibiting less severe symptomatology than males (Häfner et al, 1992; Häfner, 2003; Kulkarni et al, 2008). Deficits in selective attention are a hallmark of schizophrenia, few studies have examined whether there are sex differences in this cognitive symptom, and how ovarian hormones may contribute to such differences Preliminary research in both schizophrenic and non-schizophrenic populations, indicates that males exhibit LI under conditions where females do not (Vol’f et al, 2001; Kaplan and Lubow, 2011). The reason for these sex differences is currently unknown, but it is possible that higher levels of estrogens in females may contribute to this deficit in selective attention. Antipsychotic treatments ameliorate the deficiencies in selective attention observed in schizophrenics, but it remains unclear whether there are sex differences in this response to antipsychotic medication
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