Abstract

PI's abstract): The long-term goals of this project are to gain understanding of the means by which the brainstem mediates some of the analgesic effects of opioids. In the present proposal we concentrate on the involvement of the periaqueductal gray matter. The periaqueductal gray matter is a key structure in mediation of opioid analgesia. However, the relationship between opioid receptors, GABAergic neurons, medullary projection neurons, endogenous opioids, and opioid responses is not clear. Thus we propose the following specific aims: To determine whether axon terminals (and in particular GABAergic terminals) immunoreactive for the cloned mu-opioid receptor (MOR1) are in synaptic contact with PAG neurons projecting to the rostral ventromedial medulla (PAG-RVM neurons). In addition, to determine whether neurons hyperpolarized by opioids in the PAG are GABAergic. To determine the cellular effects in the PAG of activation of delta-opioid receptors and determine the synaptic relationship of processes immunoreactive for the cloned delta-opioid receptor (DOR1) to physiologically and anatomically characterized PAG neurons. To determine the cellular distribution of MOR1-ir and DOR1-ir in PAG-RVM neurons. To determine whether neurons responsive to mu-opioid receptors are under the synaptic control of endogenous opioid circuits. To determine the origin of MOR1 and DOR1 immunoreactive processes in the PAG. Addressing these issues will increase our knowledge of the PAG circuitry associated with antinociception. Ultimately, it is hoped that they will suggest novel clinical strategies for inducing or augmenting analgesia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA009642-08S1
Application #
6899490
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Thomas, David A
Project Start
1995-09-30
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2005-04-30
Support Year
8
Fiscal Year
2004
Total Cost
$61,400
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Neurosciences
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Gu, Ming; Wessendorf, Martin (2007) Endomorphin-2-immunoreactive fibers selectively appose serotonergic neuronal somata in the rostral ventral medial medulla. J Comp Neurol 502:701-13
Marinelli, S; Connor, M; Schnell, S A et al. (2005) delta-opioid receptor-mediated actions on rostral ventromedial medulla neurons. Neuroscience 132:239-44
Schnell, Stephen A; Wessendorf, Martin W (2004) Expression of MOR1C-like mu-opioid receptor mRNA in rats. J Comp Neurol 473:213-32
Marinelli, Silvia; Schnell, Stephen A; Hack, Stephen P et al. (2004) Serotonergic and nonserotonergic dorsal raphe neurons are pharmacologically and electrophysiologically heterogeneous. J Neurophysiol 92:3532-7
Wessendorf, M W; Wang, H; Schnell, S A (2004) Statistical methods for in situ hybridization: identification of autoradiographically labelled cells and structures. J Microsc 215:50-61
Marinelli, Silvia; Vaughan, Christopher W; Schnell, Stephen A et al. (2002) Rostral ventromedial medulla neurons that project to the spinal cord express multiple opioid receptor phenotypes. J Neurosci 22:10847-55
Wang, H; Wessendorf, M W (2002) Mu- and delta-opioid receptor mRNAs are expressed in periaqueductal gray neurons projecting to the rostral ventromedial medulla. Neuroscience 109:619-34
Peoples, James F; Wessendorf, Martin W; Pierce, Tracy et al. (2002) Ultrastructure of endomorphin-1 immunoreactivity in the rat dorsal pontine tegmentum: evidence for preferential targeting of peptidergic neurons in Barrington's nucleus rather than catecholaminergic neurons in the peri-locus coeruleus. J Comp Neurol 448:268-79
Wang, H; Wessendorf, M W (2001) Equal proportions of small and large DRG neurons express opioid receptor mRNAs. J Comp Neurol 429:590-600
Wessendorf, M W; Dooyema, J (2001) Coexistence of kappa- and delta-opioid receptors in rat spinal cord axons. Neurosci Lett 298:151-4

Showing the most recent 10 out of 19 publications