Cittadella Universitaria di Monserrato
S.S. 554, Km 4,5
09042 Monserrato (CA)
Neurosteroids and GABA-A receptors
Neurosteroids are endogenous neuromodulators that rapidly alter neuronal excitability via membrane receptors and exert anxiolytic, anticonvulsant, antidepressant, sedative, anesthetic, analgesic, rewarding and neuroprotective effects. Among these steroids, the progesterone metabolite, allopregnanolone, potentiates GABA-A receptor function and regulates GABA-A receptor expression.
Our laboratory employs neurochemical and behavioral pharmacology techniques to explore the role of neurosteroids and GABA-A receptors in physiological conditions related to development and reproduction, as well as in neuropsychiatric diseases such as emotional disorders and drug addiction.
Research projects investigate the role of neurosteroids in:
- GABA-A receptor plasticity in physiopathological conditions.
- neurochemical and behavioral effects of hormonal contraceptives.
- development and sexual differentiation of the brain.
- drug abuse and addiction.
Porcu P, Barron AM, Frye CA, Walf AA, Yang SY, He XY, Morrow AL, Panzica GC and Melcangi RC. Neurosteroidogenesis today: Novel targets for neuroactive steroid synthesis and action and their relevance for translational research. J Neuroendocrinol 28(2), 2016. PMID: 26681259.
Porcu P and Morrow AL. Divergent neuroactive steroid responses to stress and ethanol in rat and mouse strains: relevance for human studies. Psychopharmacology, 231(17): 3257-3272, 2014. PMID: 24770626.
Santoru F, Berretti R, Locci A, Porcu P and Concas A. Decreased allopregnanolone induced by hormonal contraceptives is associated with a reduction in social behavior and sexual motivation in female rats. Psychopharmacology, 231(17): 3351-3364, 2014. PMID: 24728651.
Cook JB, Werner DF, Maldonado-Devincci AM, Leonard MN, Fisher KR, O’Buckley TK, Porcu P, McCown TJ, Besheer J, Hodge CW and Morrow AL. Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3,5-THP and reduces long-term operant ethanol self-administration. J Neurosci, 34: 5824-5834, 2014. PMID: 24760842.
Porcu P, Locci A, Santoru F, Berretti R, Morrow AL and Concas A. Failure of acute ethanol administration to alter cerebrocortical and hippocampal allopregnanolone levels in C57BL/6J and DBA/2J mice. Alcohol Clin Exp Res, 38: 948-958, 2014. PMID: 24428156.
Berretti R, Santoru F, Locci A, Sogliano C, Calza A, Choleris E, Porcu P and Concas A. Neonatal exposure to estradiol decreases hypothalamic allopregnanolone concentrations and alters agonistic and sexual but not affective behavior in adult female rats. Horm Behav, 65: 142-153, 2014. PMID: 24368289.