Office: 210-567-4174
Email: morilak@uthscsa.edu

The focus of research in our laboratory is on the brain neurotransmitter norepinephrine (NE) and its role in a) actue behavioral, cognitive and endocrine resonses to stress; b) adaptive and maladaptive responses to chronic stress; and c) regulatory mechanisms of action of psychotherapeutic drugs. NE is an important neuromodulatory transmitter, which plays a critical role in the acute response to stress by influencing arousal and sensorimotor response characteristics, and by integrating autonomic and endocrine responses with behavior. Using in vivo microdialysis and behavioral pharmacology, we investigate the role of NE in modulating anxiety-like behavioral and neuroendocrine responses to acute stress, and in enhancing higher-order cognitive processes in the medial prefrontal cortex related to arousal and attention. At a molecular and cellular level, we study regulatory changes in gene expression induced in brain noradrenergic neurons in response to stress, including expression of mRNA for synthetic enzymes, the NE transporter and post-synaptic adrenergic receptors using in situ hybridization. A second project addresses changes produced by chronic stress in the brain noradrenergic system that may contribute to the development of stress-related pathology such as depression, PTSD or anxiety disorders. Another major effort is to understand the regulatory changes in NE function that contribute to the beneficial therapeutic effects of antidepressant and anxiolytic drugs. Experimental approaches include local drug microinjections into stress-related brain regions; in vivo microdialysis to measure neurotransmitter release in behaving rats; in situ hybridization, immunohistochemistry and receptor autoradiography; radioimmunoassay for plasma hormone measures; behavioral measures of cognition, arousal, anxiety and defensive responses; and the application and analysis of chronic metabolic and psychogenic stressors. These studies will help us to understand the differential roles of NE and other monoaminergic neurotransmitters in a number of complex physiological contexts, including the response to acute stress and the development of chronic stress-related psychopathology such as anxiety or depression, and also in the mechanisms of beneficial action of psychotherapeutic agents such as antidepressants.

Selected Publications

Lapiz, M.D.S., Bondi, C.O. and Morilak, D.A. (2007) Chronic treatment with desipramine improves cognitive performance of rats in an attentional set shifting test. Neuropsychopharmacology, 32:1000-1010.

Bondi, C.O., Barrera, G., Lapiz, M.D.S., Bedard, T., Mahan, A., and Morilak, D.A. (2007) Noradrenergic facilitation of shock-probe defensive burying in lateral septum of rats, and modulation by chronic treatment with desipramine. Prog. Neuropsychopharmacol. Biol. Psychiatry, 31:482-495.

Barrera, G., Poulin, J.F., Hernandez, A., Laforest, S., Drolet, G., Morilak, D.A. (2006) Galanin-mediated anxiolytic effect in rat central amygdala is not a result of co-release from noradrenergic terminals. Synapse, 59:27-40.

Lapiz, M.D. and Morilak, D.A. (2006) Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capability. Neurosci., 137:1039-1049.

Morilak, D.A., Barrera, G., Echevarria, D.J., Garcia, A.S., Hernandez, A., Ma, S., Petre, C.O. (2005) Role of brain norepinephrine in the behavioral response to stress. Prog. Neuropsychopharmacol. Biol. Psychiatr., 29:1214-1224.

Frazer, A. and Morilak, D.A. (2005) What should animal models of depression model? Neurosci. Biobeh. Revs., 29:515-523.

Echevarria, D.J., Hernandez, A., Diogenes, A., Morilak, D.A. (2005) Administration of the galanin antagonist M40 into lateral septum attenuates shock probe defensive burying behavior in rats. Neuropeptides, 39:445-451.

Ma, S. and Morilak, D.A. (2005) Chronic intermittent cold stress sensitizes the HPA response to a novel acute stress by enhancing noradrenergic influence in the rat paraventricular nucleus. J. Neuroendocrinol., 17:761-69.

Ma, S. and Morilak, D.A. (2005) Norepinephrine release in medical amygdala facilitates activation of the HPA axis in response to acute immobilization stress. J. Neuroendocrinol., 17:22-28.

Garcia, A.S., Barrera, G., Burke, T.F., Hensler, J.G. and Morilak, D.A. (2004) Autoreceptor-mediated inhibition of norepinephrine release in rat medial prefrontal cortex is maintained after chronic desipramine treatment. J. Neurochem., 91:683-693.

Ma, S. and Morilak, D.A. (2004) Induction of Fos expression by acute immobilization stress is reduced in locus coeruleus and medial amygdala of Wistar-Kyoto rats compared to Sprague-Dawley rats. Neurosci., 124:963-972.

Morilak, D.A. and Frazer, A. (2004) Antidepressants and Brain Monoaminergic Systems: A Dimensional Approach to Understanding Their Efficacy in Depression and Anxiety Disorders. Int. J. Neuropsychopharmacol., 7:193-218.

Benmansour, S., Altamirano, A.V., Jones, D.J., Sanchez, T.A., Gould, G.G., Pardon, M.-C., Morilak, D.A., Frazer, A. (2004). Regulation of the norepinephrine transporter by chronic administration of antidepressants. Biol. Psychiat., 55:313-316.

Pardon, M.-C., Ma, S. and Morilak, D.A. (2003). Chronic cold stress sensitizes brain noradrenergic reactivity and noradrenergic facilitation of the HPA stress response in Wistar Kyoto rats, Brain Res., 971:55-65.

Khoshbouei, H., Cecchi, M., Dove, S., Javors, M. and Morilak, D.A. (2002) Behavioral reactivity to stress: Amplification of stress-induced noradrenergic activation elicits a galanin-mediated anxiolytic effect in central amygdala. Pharmacol., Biochem., and Behav., 71:407-417.

Khoshbouei, H., Cecchi, M.. and Morilak, D.A. (2002) Modulatory effects of galanin in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress. Neuropsychopharmacol., 27:25-34.

Cecchi, M., Khoshbouei, H., Javors, M. and Morilak, D.A. (2002) Modulatory effects of norepinephrine in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress. Neurosci., 112:13-21.

Pardon, M.-C., Gould, G.G., Garcia, A., Phillips, L., Cook, M.C., Miller, S.A., Mason, P.A. and Morilak, D.A. (2002). Stress reactivity of the brain noradrenergic system in three rat strains differing in their neuroendocrine and behavioral responses to stress: Implications for susceptibility to stress-related neuropsychiatric disoders. Neurosci., 115:229-242.

Cecchi, M., Khoshbouei, H., and Morilak, D.A. (2002). Modulatory effects of norepinephrine, acting on alpha1-receptors in the central nucleus of the amygdala, on behavioral & neuroendocrine responses to acute immobilization stress. Neuropharmacol., 43:1139-1147.