The behavioural neuroscience division of the UBC Sexual Psychophysiology and Psychoneuroendocrinology Laboratory focuses on animal models of human psychopathology and sexual functioning through research with rats. Currently the major focus of research is concerned with understanding how the endocannabinoid system is regulated by both stress and antidepressants and how this relates to the symptomatology of depression. There are several lines of evidence that suggest that the endocannabinoid system may be involved in depression:

1. The cannabinoid receptor (CB 1 ) is located in brain regions crucial for emotionality and stress regulation such as the prefrontal cortex, hippocampus, hypothalamus and amygdala;
   
2. Genetic and pharmacological blockade of the endocannabinoid system results in a phenotypic state that is very reminiscent of depression; specifically this treatment results in increased anxiety-like and depressive-like behaviours in rodents, anhedonia (the inability to respond to rewarding stimuli), insomnia, reduced feeding and weight loss (as seen in severe depression), and sensitized responsivity to stress;
   
3. Chronic unpredictable stress, a phenomenon known to elicit depressive episodes in humans, results in a dramatic downregulation of the endocannabinoid system, suggesting a functional link between stress exposure and the induction of depression;
   
4. Several regimens that elicit an antidepressant response (pharmacological antidepressant treatment, voluntary exercise, environmental enrichment) result in an upregulation of various aspects of the endocannabinoid system;
   
5. Enhancement of endocannabinoid activity elicits antidepressant responses in preclinical animal paradigms assessing antidepressant potential. This finding is paralleled by the robust antidepressant and anti-stress effect of cannabis consumption in humans.

Together, these findings (many of them obtained through work in this laboratory) suggest that in some forms of depression, the endocannabinoid system may be compromised, and this underactivity may be responsible for the manifestation of some symptom clusters.

Published studies stemming from this research include:

Gorzalka, B.B., & Hill, M.N. (in press). Cannabinoids, reproduction and sexual behavior. Annual Review of Sex Research.

Hill, M.N., Kambo, J.S., Sun, J.C., Gorzalka, B.B., & Galea, L.A. (in press). Endocannabinoids modulate stress-induced suppression of hippocampal cell proliferation and activation of defensive behaviors. European Journal of Neuroscience.

Hill, M.N., & Gorzalka, B.B. (2006). Increased sensitivity to restraint stress and novelty-induced emotionality following long-term, high-dose cannabinoid exposure. Psychoneuroendocrinology, 31, 526-536.

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 tricyclic antidepressant treatment to suppress stress-induced activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology, May 10 [epub ahead of print].

Hill, M.N., Sun, J.C., Tse, M.T., & Gorzalka, B.B. (2006). Altered responsiveness of serotonin-receptor subtypes following long-term cannabinoid treatment. International Journal of Neuropsychopharmacology, 9, 277-286.

Gorzalka, B.B., Hill, M.N., & Sun, J.C. (2005). Functional role of the endocannabinoid system and AMPA/kainate receptors in 5-TH2A receptor-mediated wet-dog shakes. European Journal of Pharmacology, 516, 28-33.

Hill, M.N., & Gorzalka, B.B. (2005). Is there a role for the endocannabinoid system in the etiology and treatment of melancholic depression? Behavioral Pharmacology, 16, 333-352.

Hill, M.N., & Gorzalka, B.B. (2005). Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the rat forced swim test. European Neuropsychopharmacology, 15, 593-599.

Hill, M.N., Ho, W.S., Meier, S., Gorzalka, B.B., & Hillard, C.J. (2005). Chronic corticosterone treatment increases the endocannabinoid 2-arachidonylglycerol in the rat amygdala. European Journal of Pharmacology, 528, 99-102.

Hill, M.N., Patel, S., Carrier, E.J., Rademacher, D.J., Ormerod, B.K., Hillard, C.J. & Gorzalka, B.B. (2005). Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress. Neuropsychopharmacology, 30, 508-515.

Hill, M. N., Froc, D. J., Fox, C., Gorzalka, B. B. & Christie, B.R. (2004). Prolonged cannabinoid treatment results in spatial memory deficits and impaired long term potentiation in the CA 1 region of the hippocampus in vivo . European Journal of Neuroscience, 20, 859-863.

Hill, M. N. & Gorzalka, B. B. (2004). Enhancement of anxiety-like responsiveness to the cannabinoid receptor agonist HU-210 following chronic stress. European Journal of Pharmacology, 499, 291-295.

Hill, M. N., Gorzalka, B. B. & Choi, J. W. (2004). Augmentation of the development of behavioral tolerance to cannabinoid administration by Pavlovian conditioning. Neuropsychobiology, 49, 94-100.

Other Publications Related to Animal Models and Psychoneuroendocrinology:

Magyar, O., Hill, M. N., Pinel, J. P. J., & Gorzalka, B. B. (2005). Long-term kindling of the basolateral amygdala impairs copulatory behavior in male rats. Neuroscience Letters, 390, 162-165.

Gorzalka, B. B., Hanson, L., Harrington, J., Killam, S., & Campbell-Meiklejohn, P. (2003). Conditioned taste aversion: Modulation by 5-HT receptor activity and corticosterone. European Journal of Pharmacology , 471, 129-134.

Hill, M. N., Brotto, L. A., Lee, T.T-Y. & Gorzalka, B. B. (2003). Corticosterone attenuates the antidepressant-like effect elicited by melatonin in the forced swim test in both male and female rats. Progress in Neuropsychopharmacology & Biological Psychiatry, 27, 905-911.

Price, I. V., & Gorzalka, B. B. (2002). Effect of restraint stress duration on macronutrient intake in the female rat. Nutrition Research , 22, 931-943.

Brotto, L. A., Gorzalka, B. B., & Barr, A. M. (2001). Paradoxical effects of chronic corticosterone on forced swim behaviours in aged male and female rats. European Journal of Pharmacology , 424 , 203-209.

Brotto, L. A., Gorzalka, B. B., & LaMarre, A. K. (2001). Melatonin protects against the effects of chronic stress on sexual behavior in rats. NeuroReport , 12, 3465-3469.

Gorzalka, B. B., Hanson L. A., & Hong, J. J. (2001). Ketanserin attenuates the behavioral effects of corticosterone: Implications for 5-HT 2A receptor regulation. European Journal of Pharmacology , 428, 235-240.

Brotto, L. A., Barr, A. M., & Gorzalka, B. B. (2000). Sex differences in forced-swim and open-field test behaviors after chronic administration of melatonin. European Journal of Pharmacology, 402, 87-93.

Brotto, L. A., & Gorzalka, B. B. (2000). Melatonin enhances sexual behavior in the male rat. Physiology and Behavior, 68, 483-486.

Brotto, L.A., Hanson, L.A., & Gorzalka, B.B. (1999). Nefazodone attenuates the stress - induced facilitation of wet dog shaking behaviour but not the facilitation of sexual behaviour in female rats. European Journal of Pharmacology, 381, 101-104.

Gorzalka, B. B., Brotto, L. A., & Hong. J. J. (1999). Corticosterone regulation of 5-HT 2A receptor-mediated behaviours: Attenuation by melatonin . Physiology and Behavior, 67, 439-442.

Hanson, L. A., & Gorzalka, B. B. (1999). The influence of corticosterone on serotonergic stereotypy and sexual behavior in the female rat. Behavioural Brain Research, 104, 27-35.

Schulze, H. G., Greek, L. S. Barbosa, C. J., Blades, M. W., Gorzalka, B. B., & Turner, R. F. B (1999). The measurement of some small-molecule and peptide neurotransmitters in vitro and potentially in vivo with a fiber-optic probe using pulsed ultraviolet resonance Raman spectroscopy. Journal of Neuroscience Methods, 92, 15-24.

Brotto, L. A., Gorzalka, B. B., & Hanson, L. A. (1998). Effects of housing conditions and 5-HT2A activation on male rat sexual behavior. Physiology and Behavior, 63, 475-479.

Gorzalka, B. B., & Hanson, L. A. (1998). Sexual behavior and wet dog shakes in the male rat: Regulation by corticosterone. Behavioural Brain Research, 97 , 143-151.

Gorzalka, B. B., Hanson, L. A., & Brotto, L. A. (1998). Chronic stress effects on sexual behavior in male and female rats: Mediation by 5-HT2A receptors. Pharmacol Biochem Behav, 61, 405-412.

Hanson, L. A., Gorzalka, B. B., & Brotto, L. A. (1998). The antidepressant, nefazodone, attenuates corticosterone-induced increases in 5-HT2A receptor-mediated behaviors in the female rat. European Journal of Pharmacology, 342, 163-165.

Price, I. V., Gorzalka, B. B., White, S. J., & Arkinstall, K. H. (1998). Amperozide influences feeding independently of 5-HT2A receptor antagonism. Neuropsychobiology, 37 , 155-159.

Gorzalka, B. B., Heddema, G. M., Lester, G. L., & Hanson, L. A. (1997). Beta-endorphin inhibits and facilitates lordosis behaviour in rats depending on ventricular site of administration. Neuropeptides, 31 , 517-521.