Clinical studies have reported differences in the severity and incidence

Clinical studies have reported differences in the severity and incidence of schizophrenia symptoms between male and female schizophrenia patients. across the estrous cycle in the MAM rodent model of schizophrenia. We demonstrate that the elevation in dopamine neuron activity consistently observed in male MAM-treated rats is most prominent during estrus and attenuated in met-estrus. Furthermore this appears to be mediated in part by progesterone in the ventral hippocampus as increases in dopamine neuron population activity (observed in estrus) were normalized by the intra-hippocampal supervision of the progesterone NSC-207895 (XI-006) receptor antagonist mifepristone (but not the estrogen 1022150-57-7 supplier receptor antagonists fulvestrant). Taken together these data suggest that changes in dopamine system function occur across the estrous cycle in MAM-treated rats and may contribute to the differences in symptomatology between male and female schizophrenia patients. Keywords: Schizophrenia Dopamine Estrous cycle Progesterone Hippocampus Intro Schizophrenia is a devastating psychiatric condition affecting up to 1% of the US population (Bhugra 2005 Saha et al. 2005 While this disease affects both men and women there are reported differences NSC-207895 (XI-006) between genders that suggest a hormonal component to the pathophysiology of this disorder (for review see (Leung 2000 Indeed Kraepelin’s initial observations suggested differences in prevalence and symptomatology between male and female schizophrenia patients (Kraepelin 1919 Since this time it has been demonstrated that males have an earlier onset of the disease (Aleman et al. 2003 a greater degree of premorbid deficits (Larsen et al. 1996 and significant differences in symptom severity (Leung 2000 For example females are reported to display relatively greater positive symptom severity (auditory hallucinations & persecutory delusions) while males show enhanced negative and cognitive dysfunction (specifically those involved in verbal processing) (Goldstein et al. 1998 Leung 2000 In addition NSC-207895 (XI-006) female patients have been demonstrated to show a more rapid and greater response to antipsychotic medications (Szymanski et al. 1995 While this appears to be true for both typical and atypical antipsychotics gender differences are more evident with clozapine when compared to olanzapine or risperidone (Usall et al. 2007 The consequence of this is that females are reported to require significantly reduce doses as well as requiring longer intervals intended for depot supervision (Seeman 2004 Interestingly a meta-analysis of structural imaging studies demonstrate that effect size is unrelated to gender suggesting a similar pattern of structural alterations in male and female patients and arguing against the idea of different pathological processes in the two genders (Wright et al. 2000 Taken together these data suggest that while the structural alterations occurring in schizophrenia patients are not related to gender hormonal regulation of these key neuronal structures may result in differences in symptomatology and pharmaceutical efficacy. While the pathophysiology of schizophrenia has not been 1022150-57-7 supplier conclusively demonstrated an enhanced dopamine signaling is one of the more prominent hypotheses from the disease (Laruelle and Abi-Dargham 1999 Abi-Dargham 2004 Imaging studies have consistently demonstrated region particular NSC-207895 (XI-006) increases in dopamine indication in people whereas the efficacy of dopamine radio antagonists for the disease supplies further support for this theory. Consistent with 1022150-57-7 supplier this kind of NSC-207895 (XI-006) hypothesis we now have previously showed a another increase in dopamine neuron Rabbit Polyclonal to ADA2L. activity in the methylazoxymethanol acetate (MAM) rodent type of schizophrenia (Lodge and Grace 3 years ago Perez 1022150-57-7 supplier and Lodge 2013 Perez ain al. 2013 The MAM model can be described as developmental interruption model with strong confront and predictive validity (Moore and Grace 2002 Lodge and style 2009 Particularly MAM-treated rodents display histological alterations in line with those recognized postmortem in schizophrenia (Moore et ‘s. 2006 Villa et ‘s. 2009 Moreover MAM-treated rodents display changes in.