Distribution of CB1 cannabinoid receptors and their relationship with mu-opioid receptors in the rat periaqueductal gray

Abstract

The periaqueductal gray (PAG) is part of a descending pain modulatory system that, when activated, produces widespread and profound antinociception. Microinjection of either opioids or cannabinoids into the PAG elicits antinociception. Moreover, microinjection of the cannabinoid 1 (CB1) receptor agonist HU-210 into the PAG enhances the antinociceptive effect of subsequent morphine injections, indicating a direct relationship between these two systems. The objective of this study was to characterize the distribution of CB1 receptors in the dorsolateral and ventrolateral PAG in relationship to mu-opioid peptide (MOP) receptors. Immunocytochemical analysis revealed extensive and diffuse CB1 receptor labeling in the PAG, 60% of which was found in somatodendritic profiles. CB1 and MOP receptor immunolabeling were co-localized in 32% of fluorescent Nissl-stained cells that were analyzed. Eight percent (8%) of PAG neurons that were MOP receptor-immunoreactive received CB1 receptor-immunoreactive appositions. Ultrastructural analysis confirmed the presence CB1 receptor-immunoreactive somata, dendrites and axon terminals in the PAG. These results indicate that behavioral interactions between cannabinoids and opioids may be the result of cellular adaptations within PAG neurons co-expressing CB1 and MOP receptors.

Song-associated reward correlates with endocannabinoid-related gene expression in male European starlings ( Sturnus vulgaris )

“…The results of the current study indicate a negative linear relationship between CB 1 and song-associated reward. MOR and CB 1 receptors co-localize in PAG (Wilson-Poe et al, 2012), so it is possible that our results are highlighting the negative portion of the curve found by Kelm-Nelson and Riters (2013). However, double-labeling studies examining MOR and CB 1 receptors in PAG in males producing undirected song are needed.…”

Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in mouse neuropathic and inflammatory pain models

“…While the present study did not assess whether cannabinoid receptors play a role in the anti-allodynic effects of this combination in the CCI model, previous reports indicate that both cannabinoid receptors contribute to the anti-allodynic effects of FAAH inhibitors in both the carrageenan and CCI assays (Russo, Loverme et al 2007; Kinsey, Long et al 2009; Kinsey, Long et al 2010; Ghosh, Wise et al 2013). CB 1 receptors are present in the periaqueductal grey (Wilson-Poe, Morgan et al 2012), as well as other areas involved in pain including cingulate cortex, rostral ventromedial medulla, dorsal horn, and dorsal root ganglia (Herkenham, Lynn et al 1990). CB 2 receptors are known to be associated with immune tissue, microglia and play a role in inflammation (Wotherspoon, Fox et al 2005; Racz, Nadal et al 2008; Romero-Sandoval, Nutile-McMenemy et al 2008; Rom and Persidsky 2013).…”

Differential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice

“…Furthermore, the α2 adrenergic agonist clonidine, which is known to reduce opioid withdrawal in humans (Gold et al, 1978; Gossop, 1988), attenuates opioid withdrawal CPA (Kosten, 1994; Schulteis et al, 1998a). Given the colocalization of CB 1 and mu opioid receptors in the locus coeruleus (Scavone et al, 2010), periaqueductal grey (Wilson-Poe et al, 2012) and nucleus accumbens (Pickel et al, 2004), cannabinoid receptors are advantageously positioned to compensate for the hyperactivity in neurons that are key to the expression of both somatic and aversive aspects of opioid withdrawal (Frenois et al, 2002; Lane-Ladd et al, 1997; Nestler and Tallman, 1988; Stinus et al, 1990; Widnell et al, 1994). …”