Research Interests
My research is primarily focused on understanding the role of neuroactive steroids in physiological and pathological conditions with particular regard to neuropsychiatric diseases including drug abuse and alcoholism.
My current research is focused on understanding the relationship between stress responses, alcohol consumption and neuroactive steroids in mice, rats, non-human primates and humans. The brain and plasma concentrations of GABAergic neuroactive steroids are increased by acute stress and ethanol administration in rodents. The stress- and ethanol-induced increases in neuroactive steroid levels are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, since they are no longer observed in adrenalectomized/gonadectomized animals. Dysregulation of the HPA axis is also associated to several neuropsychiatric disorders, including depression, post-traumatic stress disorder or premenstrual syndrome. My most recent work showed that plasma levels of two neuroactive steroids, deoxycorticosterone and pregnenolone, are differentially regulated by various challenges to the HPA axis in ethanol-naïve cynomolgus monkeys. This work also showed that neuroactive steroid responses to HPA axis challenges in ethanol-naïve monkeys may predict subsequent alcohol consumption. Dexamethasone suppression of plasma deoxycorticosterone levels was negatively correlated with the average daily ethanol intake during the subsequent one-year period of ethanol self-administration. That is, monkeys who drank the most alcohol exhibited weaker suppression of deoxycorticosterone levels by dexamethasone when tested prior to any alcohol exposure.
I am currently exploring the relationship between dexamethasone suppression of deoxycorticosterone levels and subsequent voluntary alcohol consumption. The goal is to extend the finding in non-human primates to the BXD recombinant inbred mice and their parental strains C57BL/6J and DBA/2J. The hypothesis is that dexamethasone suppression of plasma and brain deoxycorticosterone levels will be related to a network of alcohol- and stress-related phenotypes that will provide new insights into alcohol/stress interactions. Genetic analysis on these data will allow finding of genetic markers and trait covariates associated with susceptibility to stress and alcohol abuse. In my future studies, I am interested in the combination of neuroactive steroids effects and genetics, to advance the field in a new and unique way.
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Recent Publications
(Click for a list of publications from PubMed)
The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress. Kumar S, Porcu P, Werner DF, Matthews DB, Diaz-Granados JL, Helfand RS, Morrow AL. Psychopharmacology (Berl).
Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Marx CE, Keefe RS, Buchanan RW, Hamer RM, Kilts JD, Bradford DW, Strauss JL, Naylor JC, Payne VM, Lieberman JA, Savitz AJ, Leimone LA, Dunn L, Porcu P, Morrow AL, Shampine LJ. Neuropsychopharmacology. 2009 Jul;34(8):1885-903.
Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum. Porcu P, O'Buckley TK, Alward SE, Marx CE, Shampine LJ, Girdler SS, Morrow AL. Steroids. 2009 Apr-May;74(4-5):463-73.
Porcu P, O'Buckley TK, Leslie Morrow A, Adinoff B. Differential hypothalamic-pituitary-adrenal activation of the neuroactive steroids pregnenolone sulfate and deoxycorticosterone in healthy controls and alcohol-dependent subjects.Psychoneuroendocrinology. 2008 Feb;33(2):214-26.
Sassoè-Pognetto M, Follesa P, Panzanelli P, Perazzini AZ, Porcu P, Sogliano C, Cherchi C, Concas A. Fluctuations in brain concentrations of neurosteroids are not associated to changes in gephyrin levels. Brain Res. 2007 Sep 12;1169:1-8.
Morrow AL, Porcu P, Boyd KN, Grant KA. Hypothalamic-pituitary-adrenal axis modulation of GABAergic neuroactive steroids influences ethanol sensitivity and drinking behavior.Dialogues Clin Neurosci. 2006;8(4):463-77.
Porcu P, Rogers LS, Morrow AL, Grant KA. Plasma pregnenolone levels in cynomolgus monkeys following pharmacological challenges of the hypothalamic-pituitary-adrenal axis.Pharmacol Biochem Behav. 2006 Aug;84(4):618-27.
Concas A, Sogliano C, Porcu P, Marra C, Brundu A, Biggio G. Neurosteroids in nicotine and morphine dependence.Psychopharmacology (Berl). 2006 Jun;186(3):281-92. Epub 2005 Aug 17.
Porcu P, Grant KA, Green HL, Rogers LS, Morrow AL. Hypothalamic-pituitary-adrenal axis and ethanol modulation of deoxycorticosterone levels in cynomolgus monkeys.Psychopharmacology (Berl). 2006 Jun;186(3):293-301.
Shannon EE, Porcu P, Purdy RH, Grant KA. Characterization of the discriminative stimulus effects of the neuroactive steroid pregnanolone in DBA/2J and C57BL/6J inbred mice.J Pharmacol Exp Ther. 2005 Aug;314(2):675-85.
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Bowles Center for Alcohol Studies at the University of North Carolina at Chapel Hill