Effects of some psychiatric drugs on corticotropin-releasing factor (CRF) gene expression in mouse hypothalamus cells in vitro
Keywords:
Psychiatric drugs, HPA, CRFAbstract
Psychiatric drugs are typically used to treat patients suffered from mental disorders and some conditions of stress-related disorders. Effects of psychiatric drugs actions were proposed to be involved in regulation of neuronal gene expression. One of the genes involved is corticotropin-releasing factor (CRF) gene that plays a critical role in controlling the hypothalamus-pituitary-adrenal (HPA) axis under stress condition. This study aims to examine the effects of psychiatric drugs on CRF gene expression in a mouse hypothalamus cell line. Quantitative real-time PCR was used to determine expression levels of CRF gene in cells treated with diazepam, risperidone and haloperidol. Results showed that all of the drugs tested tend to suppress CRF gene expression at the RNA levels, both before and after the cells were incubated with forskolin, a stress-inducing agent. The findings suggested that the mechanism of psychiatric drugs actions may act in HPA negative-feedback control by regulating CRF mRNA expression in response to stress.
References
Braff DL, Grillon C, Geyer MA (1992) Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49: 206–215.
Braff DL, Geyer MA, Swerdlow NR (2001). Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl) 156: 234–258.
Brayfield A (2013) Haloperidol. Martindale: The Complete Drug Reference. Pharmaceutical Press, London, UK.
Bremner JD, Licinio J, Darnell A, Krystal JH, Owens MJ, Southwick SM, Nemeroff CB, Charney DS (1997) Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder. Am J Psychiatry 154: 624–629.
Brunton L, Chabner B, Knollman B (2010) Goodman and Gilman’s the pharmacological basis of therapeutics. 12th ed. McGraw Hill Professional, New York.
Budziszewska B, Jaworska-Feil L, Tetich M, Basta-Kaim A, Kubera M, Leskiewicz M, Lasoñ W (2002) Effect of antidepressant drugs on the human corticotrophin-releasing-hormone gene promoter activity in neuro-2A cells. Pol J Pharmacol 54: 711–716.
Budziszewska B, Jaworska-Feil L, Tetich M, Basta-Kaim A, Kubera M, Leoekiewicz M, Lason W (2004) Regulation of the human corticotropin-releasing-hormone gene promoter activity by antidepressant drugs in Neuro-2A and AtT-20 Cells. Neuropsychopharmacology 29: 785–794.
Dirks A, Groenink L, Westphal KGC, Olivier JDA, Verdouw PM, van der Gugten J, Geyer MA, Olivier B (2003) Reversal of startle gating deficits in transgenic mice overexpressing corticotropin-releasing factor by antipsychotic drugs. Neuropsychopharmacology 28: 1790–1798.
Ereshefsky L, Davis CM, Harrington CA, Jann MW, Browning JL, Saklad SR, Burch NR (1984) Haloperidol and reduced haloperidol plasma levels in selected schizophrenic patients. J Clin Psychopharmacol 4: 138–142.
Grillon C, Morgan CA, Davis M, Southwick SM (1998) Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder. Biol Psychiatry 44: 1027–1036.
Guardiola-Diaz HM, Boswell C, Seasholtz AF (1994) The cAMP-responsive element in the corticotropinreleasing hormone gene mediates transcriptional regulation by depolarization. J Biol Chem 269: 14784–14791.
Itoi K, Horiba N, Tozawa F, Sakai Y, Sakai K, Abe K, Demura H, Suda T (1996) Major role of 3’5’-cyclic adenosine monophosphate-dependent protein kinase A pathway in corticotropin-releasing factor gene expression in the rat hypothalamus in vivo. Endocrinology 137: 2389–2396.
Kageyama K, Hanada K, Takayasu S, Iwasaki Y, Sakihara S, Nigawara T, Suda T (2008) Involvement of regulatory elements on corticotropin-releasing factor gene promoter in hypothalamic 4B cells. J Endocrinol Invest 31: 1079–1085.
Kirino E (2014) Efficacy and tolerability of pharmacotherapy options for the treatment of irritability in autistic children. Clin Med Insights Pediatr 8: 17–30.
Lakic N, Pericic D, Maney H (1986) Mechanism by which picrotoxin and a high dose of diazepam elevate plasma corticosterone level. Neuroendocrinology 43: 331–335.
Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, et al. (2013) Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382(9896): 951–962.
McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonte B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12: 342–348.
Meloni EG, Gerety LP, Knoll AT, Cohen BM, Carlezon Jr WA (2006) Behavioral and anatomical interactions between dopamine and corticotropin-releasing factor in the rat. J Neurosci 26(14): 3855-3863.
Mitchell AJ (1998) The role of corticotropin releasing factor in depressive illness: a critical review. Neurosci Biobehav Rev 22(5): 635–651.
Moulin MA, Davy JP, Debruyne D, Andersson JC, Bigot MC, Camsonne R, Poilpre E (1982) Serum level monitoring and therapeutic effect of haloperidol in schizophrenic patients. Psychopharmacol 76: 346–350.
Muralidharan K, Ali M, Silveira LE, Bond DJ, Fountoulakis KN, Lam RW, Yatham LN (2013) Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: a meta-analysis of placebo-controlled trials. J Affect Disord 150(2): 408–414.
Owens M, Nemeroff C (1991) Physiology and pharmacology of corticotropinreleasing factor. Pharmacol Rev 43: 425–473.
Park SW, Choi SM, Lee JG, Lee CH, Lee SJ, Kim NR, Kim YH (2011) Differential effects of ziprasidone and haloperidol on immobilization-stress-induced CRF mRNA expression in the hypothalamic paraventricular nucleus of rats. Neuropsychobiology 63: 29–34.
Pelleymounter M, Joppa M, Carmouche M, Cullen MJ, Brown B, Murphy B, Grigoriadis DE, Ling N, Foster AC (2000) Role of corticotropin-releasing factor (CRF) receptors in the anorexic syndrome induced by CRF. J Pharm Exp Ther 293: 799–806.
Perroud N, Paoloni-Giacobino A, Prada P, Olie E, Salzmann A, Nicastro R, Guillaume S, Mouthon D, Stouder C, Dieben K, et al. (2011) Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl Psychiatry 1: e59.
Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9): e45.
Pivac N, Pericic D (1993) Inhibitory effect of diazepam on the activity of the hypothalamic-pituitary-adrenal axis in female rats. J Neural Transm 92: 173–186.
Reidenberg MM, Levy M, Warner H, Coutinho CB, Schwartz MA, Yu G, Cheripko J (1978) Relationship between diazepam dose, plasma level, age, and central nervous system depression. Clin Pharmacol Ther 23: 371–374.
Riss J, Cloyd J, Gates J, Collins S (2008) Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand 118(2): 69–86.
Seasholtz AF, Thompson RC, Douglass JO (1988) Identification of a cyclic adenosine monophosphate-responsive element in the rat corticotropin-releasing hormone gene. Mol Endocrinol 2: 1311–1319.
Sharma A, Shaw SR (2012) Efficacy of risperidone in managing maladaptive behaviors for children with autistic spectrum disorder: a meta-analysis. J Pediatr Health Care 26(4): 291–299.
Stout SC, Owens MJ, Nemeroff CB (2002) Regulation of corticotropin-releasing factor neuronal systems and hypothalamic-pituitary-adrenal axis activity by stress and chronic antidepressant treatment. J Pharmacol Exp Ther 300: 1085–1092.
Swerdlow NR, Geyer MA, Vale WW, Koob GF (1986) Corticotropin-releasing factor potentiates acoustic startle in rats: blockade by chlordiazepoxide. Psychopharmacology (Berl) 88: 147-152.
Toufexis DJ, Davis C, Hammond A, Davis M (2004)
Progesterone attenuates corticotropin-releasing factor-enhanced but not fear-potentiated startle via the activity of its neuroactive metabolite, allopregnanolone. J Neurosci 24: 10280-10287.
Vargas ML, Abella C, Hernandez J (2001) Diazepam increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity by a cyclic AMP-dependent mechanism. Br J Pharmacol 133: 1355–1361.
Vermetten E, Bremner JD (2002a) Circuits and systems in stress. II. Applications to neurobiology and treatment in posttraumatic stress disorder. Depress Anxiety 16: 14-38.
