Scientific Online Resource System

Scripta Scientifica Medica

Localization of cb1 receptors in rat`s periaqueductal gray after immobilization stress and effects of peptide tyr-w-mif- 1. immunocytochemical study

Lina Malinova, Hristina Nocheva, Adriana Bocheva, Boycho Landzhov, Elena Dzambazova, Anastasia Bozhilova-Pastirova


Periaqueductal gray (PAG) is a midbrain structure closely involved in the stress-induced analgesia. It suppresses nociception by the descending efferent pathways to the dorsal horn of the spinal cord. Except stimulation of opioid receptors, the PAG is specialized to produce cannabinoid-mediated stress-induced analgesia. Attractive candidates for opiate modulators are neuropeptides from Tyr-MIF-1 family. These peptides also are involved in the development of stress. Based on behavioral and anatomical data about direct interactions of cannabinoid type 1 (CB1) receptors and μ-receptors in the PAG we decided to investigate the effects of the Tyr-W-MIF-1 neuropeptide on expression of CB1 immunoreactive neurons in rat`s PAG after immobilization stress. Light microscopic study was used to determine the distribution of CB1 receptor immunoreactivity. The obtained results showed that stress itself increased the expression of CB1 immunoreactive neurons in the PAG compared with intact animals, while Tyr-W-MIF-1 decreased stress-induced CB1 expression mentioned above probably by opioid/cannabinoid interaction. Further studies are needed to understand the exact role of Tyr-W-MIF-1 on CB1 receptors in response to immobilization stress.


PAG; CB 1 receptors; neuropeptides; immobilization stress; Tyr-W-MIF-1

Full Text


Katona I., B .Sperlagh, A. Sik, A. Kafalvi, E.S.

Vizi, K. Mackie, T.F. Freund. Presynaptically

located CB1 cannabinoid receptors regulate

GABA release from axon terminals of specific

hippocampal interneurons. J. Neurosci., 19, 1999,

No11, 4544-4558.

Tsou K., K. Mackie, M.C. Sanudo-Pena, J.M.

Walker. Cannabinoid CB1 receptors are localized

primarily on cholecystokinin-containing

GABAergic interneurons in the rat hippocampal

formation. Neurosci., 93, 1999, No 3, 969-975.

Rodriguez J.J., K. Mackie, V.M. Pickel.

Ultrastructural localization of the CB1

cannabinoidreceptor in μ-opioid receptor patches

of the rat caudate putamen nucleus. J. Neurosci.,

, 2001, No 3, 823-833.

Bandler R., K. A. Keay, N. Floyd, J. Price. Central

circuits mediating patterned autonomic activity

during active vs. passive emotional coping. Brain

Research Bulletin, 53, 2000, No 1, 95-104.

Wilson R. I., R. A. Nicoll. Endogenous

cannabinoids mediate retrograde signalling at

hippocampal synapses. Nature, 410, 2001, No

, 588-592.

Basbaum A.I., H.L. Fields. Annu. Rev. Neurosci., 7,

, 309-338.

Xing Xing J., J. J. Li. Endogenous pain control

systems: brainstem spinal pathways and

endorphin circuitry. Neurophysiol., 97, 2007,


Butler R.K., D.P. Finn. Stress- induced analgesia.

Prog. Neurobiol., 88, 2009, No 3, 184-202.

Bocheva A, E. Dzambazova-Maximova.

Antiopioid properties of the TYR-MIF-1 family.

Methods Find Exp. Clin. Pharmacol., 26, 2004, No

, 673- 677.

Bocheva A, E. Dzambazova-Maximova. Effects of

Tyr-MIF`s family of peptides on immobilization

stress-induced antinociception in rats. Folia Med

(Plovdiv), 46, 2004, No 2, 42- 46.

Bocheva, A., E. Dzambazova-Maximova, N.

Lambadjieva. Interaction between peptides of

Tyr-MIF-1 family, morphine and nitric oxide in

nociception. Compt. Rend. Bulg. Acad. Sci., 57,

, No 3, 97-102.

Von Bohlen und Halbach O., R. Dermietzel.

In: Neurotransmitters and neu- romodulators:

Handbook of receptors and biological Efects (2nd

Ed.), Weinheim, Wiley-VCH Verlag GmbH & Co.

KgaA, 2006, 347-349.

13. Hohmann A.G., R.L. Suplita, N.M. Bolton,

M.H. Neely, D. Fegley, R. Mangieri, J.F. Krey, J.M.

Walker, P.V. Holmes, J.D. Crystal, A. Duranti,

A. Tontini, M. Mor, G. Tarzia, Piomelli D. An

endocannabinoid mechanism for stressinduced

analgesia. Nature, 435, 2005, No 7045, 1108- 1112.

Tsou K., S. Brown, M.C. Sanudo-Pena, K. Mackie,

J.M. Walker. Immunohistochemical distribution

of cannabinoid CB1 receptors in the rat central

nervous system. Neurosci., 83, 1998, No 2,


Abrams D.I., P.Couey, S.B. Shade, M.E. Kelly, N.L.

Benowitz. Cannabinoid-opioid interaction in

chronic pain. Clin. Pharmacol. Ther. 90, 2011, No

, 844- 851.

Fattore L., D. Vigano, P. Fadda, T. Rubino, W.

Fratta, D. Parolaro. Bidirectional regulation of

mu-opioid and CB1-cannabinoid receptor in rats

self-administering heroin or WIN 55,212-2. Eur J

Neurosci., 25, 2007, No 7, 2191- 2200.

Smith P.A., D.E. Selley, L.J. Sim-Selley, S.P.

Welch. Low dose combination of morphine

and delta9-tetrahydrocannabinol circumvents

antinociceptive tolerance and apparent

desensitization of receptors. Eur. J. Pharmacol.,

, 2007, No 2-3, 129- 137.

Wilson A., L. Maher, M. Morgan. Repeated

cannabinoid injections into the rat periaqueductal

gray enhance subsequent morphine

antinociception. Neuropharmacol. 55, 2008, No 7,

- 1225.

Wilson R.I., R.A. Nicoll. Endocannabinoid

signaling in the brain. Science, 296, 2002, No

, 678-682.

Alger B.E. Retrograde signaling in the

regulation of synaptic transmission: focus on

endocannabinoids. Prog Neurobiol, 68, 2002, No

, 247- 286.

Article Tools
Email this article (Login required)
About The Authors

Lina Malinova
Medical University of Sofia

Department of Anatomy, Histology and Embryology

Hristina Nocheva
Medical university of Sofia

Department of pathophysiology

Adriana Bocheva
Medical university of Sofia

Department of pathophysiology

Boycho Landzhov


Department of anatomy, histology and embryology

Elena Dzambazova
University of Sofia

Department of physiology and pathophysiology

Anastasia Bozhilova-Pastirova
Department of anatomy, histology and embryology

Font Size