are the brains endogenous version of THC, the psychoactive constituent
of cannabis (similar to how endorphins are the body’s endogenous
version of morphine). Over the past few years I have been interested
in the role of the endocannabinoid system in the regulation of stress
and emotional behavior. Research from us, and others, has demonstrated
that endocannabinoid signaling largely acts to decrease stress responses.
Deficits in endocannabinoid signaling in rodents can increase neuroendocrine
and behavioral responses to stress, and in humans, disruption of
endocannabinoid signaling can produce symptoms of depression and
anxiety. Interestingly, we have demonstrated that stress can mobilize
endocannabinoid signaling, and that this increase in endocannabinoid
signaling is required for both the normal recovery from acute stress
as well as the larger adaptive processes that occur following repeated
exposure to stress. More so, we have found that under conditions
of chronic stress, endocannabinoid signaling “breaks down”,
and that the loss of this buffer system may be one of the mechanisms
by which chronic stress increases the risk of affective illnesses,
such as depression and anxiety disorders. This hypothesis has been
supported by translational clinical studies we have performed demonstrating
that circulating levels of endocannabinoids are reduced individuals
afflicted with major depression.
focus of research in my laboratory is to understand the role of
the endocannabinoid system in the effects of stress and glucocorticoids.
Within this focus, my research is particularly interested in determining
the role of the endocannabinoid system in the effects of stress
on a) neuroendocrine function; b) emotional behaviour; c) energy
balance and metabolism; d) neuroinflammation and neurodegeneration.
This is achieved through a systems level approach incorporating
a range of neuroscientific techniques ranging from cellular to behavioural.
In particular, we employ biochemical and pharmacological techniques,
such as radioligand receptor binding and signalling assays, enzyme
activity assays, lipid mass spectrometry, gene expression analysis
and protein quantification through ELISA’s. In addition we
also perform a range of microscope techniques employing neuro-stereology
(3-dimensional neuronal reconstructions to examine dendritic architecture),
immunohistochemistry and immunofluorescence. To compliment this,
we also employ a range of behavioral techniques, ranging from fear
conditioning to the examination of basic emotional and cognitive
SIGNIFICANT RESEARCH and/or PUBLICATIONS
Hill, M.N., Hillard,
C.J., McEwen, B.S. (2011). Alterations in Corticolimbic Dendritic
Morphology and Emotional Behavior in Cannabinoid CB1 Receptor Deficient
Mice Parallel the Effects of Chronic Stress. Cerebral Cortex 21(9),
Hill, M.N., McLaughlin,
R.J., Pan, B., Fitzgerald, M.F., Roberts, C.J., Lee, T.T., Karatsoreos,
I.N., Mackie, K., Viau, V., Pickel, V., McEwen. B.S., Liu, Q.S.,
Gorzalka, B.B., Hillard, C.J. (2011). Recruitment of Prefrontal
Cortical Endocannabinoid Signaling by Glucocorticoids Contributes
to Termination of the Stress Response. Journal of Neuroscience 31(29),
Krebs-Kraft, D.L., Hill,
M.N., Hillard, C.J., McCarthy, M.M. (2010). Sex Difference in Cell
Proliferation in Developing Rat Amygdala Mediated by Endocannabinoids
has Implications for Social Behavior. Proceedings of the National
Academy of Sciences USA 107(47), 20535-20540.
Hill, M.N., Patel, S.,
Campolongo, P., Tasker, J.G., Wotjak, C.T., Bains, J.S. (2010).
Functional Interactions Between Stress and the Endocannabinoid System:
From Synaptic Signaling to Behavioral Ouput. Journal of Neuroscience
Evanson, N.K., Tasker,
J.G., Hill, M.N., Ulrich-Lai, Y.M., Hillard, C.J., Herman, J.P.
(2010). Fast-feedback Inhibition of the HPA Axis by Glucocorticoids
is Mediated by Endocannabinoid Signaling. Endocrinology 151(10),
Hill, M.N., McLaughlin,
R.J., Bingham, B., Shrestha, L., Lee, T.T., Gray, J.M., Hillard,
C.J., Gorzalka, B.B., Viau, V. (2010). Endogenous Cannabinoid Signaling
is Essential for Stress Adaptation. Proceedings of the National
Academy of Sciences USA 107(20), 9406-9411.
Hill, M.N., Titterness,
A.K., Morrish, A.C., Carrier, E.J., Lee, T.T.-Y., Gil-Mohapel, J.,
Gorzalka, B.B., Hillard, C.J., Christie, B.R. (2010). Endogenous
Cannabinoid Signaling is Required for Voluntary Exercise-induced
Enhancement of Progenitor Cell Proliferation in the Hippocampus.
Hippocampus 20(4), 513-523. (featured in the New York Times: http://well.blogs.nytimes.com/2011/02/16/phys-ed-what-really-causes-runners-high/)
Hill, M.N., McLaughlin,
R.J., Morrish, A.C., Viau, V., Floresco, S.B., Hillard, C.J., Gorzalka,
B.B. (2009). Suppression of Amygdalar Endocannabinoid Signaling
by Stress Contributes to Activation of the Hypothalamic-Pituitary-Adrenal
Axis. Neuropsychopharmacology 34(13), 2733-2745.
Hill, M.N., Miller, G.E.,
Carrier, E.J., Gorzalka, B.B., Hillard, C.J. (2009). Circulating
Endocannabinoids and N-Acyl Ethanolamines are Differentially Regulated
in Major Depression and Following Exposure to Social Stress. Psychoneuroendocrinology
Hill, M.N., Gorzalka,
B.B. (2009). Impairments in Endocannabinoid Signaling and Depressive
Illness. JAMA - Journal of the American Medical Association 301
Hill, M.N., McEwen, B.S.
(2009). Endocannabinoids: The Silent Partner of Glucocorticoids
in the Synapse. Proceedings of the National Academy of Sciences
USA 106 (12), 4579-4580.
Hill, M.N., Ho, W.S.,
Sinopoli, K.J., Viau, V., Hillard, C.J., Gorzalka, B.B. (2006).
Involvement of the Endocannabinoid System in the Ability of Long-term
Tricylic Antidepressant Treatment to Suppress Stress-induced Activation
of the Hypothalamic-Pituitary-Adrenal Axis. Neuropsychopharmacology
Hill, M.N, Patel, S.,
Carrier, E., Rademacher, D.J., Ormerod, B.K, Hillard, C.J. Gorzalka,
B.B. (2005). Down-regulation of Endocannabinoid Signaling in the
Hippocampus Following Chronic Unpredictable Stress. Neuropsychopharmacology
30 (3), 508-515.
Tel: (403) 220-6617