CB1-cannabinoid and μ-opioid receptor co-localization on postsynaptic target in the rat dorsal horn

Salio, Chiara; Fischer, Jacqueline; Franzoni, Maria Fosca; Mackie, Ken; Kaneko, Takeshi; Conrath, M.

doi:10.1097/00001756-200112040-00017

Cited by 149 publications

(90 citation statements)

References 22 publications

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“…‡ ‡ Cross-talk between MOR and CB1 is also suggested by findings in rats that heroin reinstates cannabinoid-seeking behavior (17) and that the CB1 agonist HU-210 reinstates heroin-seeking behavior (18). Consistent with these observations, CB1 and MOR are coexpressed in the NAc (19), and several investigators propose that cannabinoids and opioids may interact at cellular (20) and intracellular signaling levels (21,22). However, the postsynaptic molecular mechanisms that enable a signaling interaction between MOR and CB1 in NAc neurons are poorly understood.…”

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confidence: 63%

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Adenosine A2a blockade prevents synergy between μ-opiate and cannabinoid CB1 receptors and eliminates heroin-seeking behavior in addicted rats

Yao

McFarland

Fan

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Relapse is the most serious limitation of effective medical treatment of opiate addiction. Opiate-related behaviors appear to be modulated by cannabinoid CB1 receptors (CB1) through poorly understood cross-talk mechanisms. Opiate and CB1 receptors are coexpressed in the nucleus accumbens (NAc) and dorsal striatum. These regions also have the highest density of adenosine A2a receptors (A2a) in the brain. We have been investigating the postsynaptic signaling mechanisms of -opiate receptors (MORs) and CB1 receptors in primary NAc͞striatal neurons. In this article, we present evidence that MOR and CB1 act synergistically on cAMP͞PKA signaling in NAc͞striatal neurons. In addition, we find that synergy requires adenosine and A2a. Importantly, an A2a antagonist administered either directly into the NAc or indirectly by i.p. injection eliminates heroin-induced reinstatement in rats trained to self-administer heroin, a model of human craving and relapse. These findings suggest that A2a antagonists might be effective therapeutic agents in the management of abstinent heroin addicts.PKA ͉ addiction ͉ nucleus accumbens ͉ gene activation O piate addiction is a world-wide public health problem with serious socioeconomic ramifications. A major limitation of effective medical treatment is the craving and relapse that develops during attempted abstinence. Opiates bind to three opioid receptors: the ␦-opioid receptor (DOR), -opioid receptor (MOR), and -opioid receptor (KOR) receptors. MOR and DOR are implicated in reward for heroin and morphine, whereas KOR is implicated in aversion (1). MOR antagonists reduce opiate selfadministration, and constitutive deletion of the MOR attenuates opiate-induced conditioned place preference (CPP) (2, 3). Moreover, selective MOR blockade is sufficient to induce conditioned aversion in morphine-dependent animals, presumably because of unopposed activation of KOR (1). The nucleus accumbens (NAc) mediates reward and reinforcement of addictive agents. Thus, inactivation of the NAc core inhibits heroin self-administration (4). We have been investigating postsynaptic signaling mechanisms activated by opiate receptors in NAc͞striatal neurons. We reported that brief exposure of primary NAc͞striatal neurons to MOR agonists for 10 min activates cAMP͞PKA signal transduction followed by stimulation of cAMP response element (CRE)-mediated gene expression hours later (5). We also found that paradoxical stimulation of cAMP͞PKA signaling by G i -coupled MOR depends on preferential binding of the MOR to G␣ i3 ␤␥. Thus, activation of the MOR appears to release ␤␥ subunits from G␣ i3 ; released unbound ␤␥ subunits stimulate adenylyl cyclase (AC) II and IV to increase cAMP production. In turn, this transient increase in cAMP activates PKA and CRE-dependent gene transcription (5).Signaling of G protein-coupled receptors can be modulated by G protein regulators. Recent evidence suggests that an activator of G protein signaling 3 (AGS3), regulates G␣ i3 -coupled receptor signaling by competing with ␤␥ subunits for bin...

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confidence: 63%

“…MOR and CB1 are also expressed postsynaptically on the same medium spiny neurons (19). The unique coexpression of A2a with MOR and CB1 on the same NAc͞striatum neurons suggests that A2a might interact with and affect MOR-and CB1-addictive behavior.…”

Section: Discussionmentioning

confidence: 98%

Adenosine A2a blockade prevents synergy between μ-opiate and cannabinoid CB1 receptors and eliminates heroin-seeking behavior in addicted rats

Yao

McFarland

Fan

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Although postsynaptic CB 1 receptors have been suggested to exist in the brain (2,35,(42)(43)(44), there is no evidence that CB 1 receptors located postsynaptically influence GABA transporter function. Furthermore, Vaughan et al (53) did not find postsynaptic cannabinoid inhibition in the PAG, which is consistent with the observation of a high prevalence of CB 1 receptors on PAG axons and fibers rather than cell bodies (52).…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB₁ receptors

Fu¹,

Longhurst²

2009

Journal of Applied Physiology

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Fu L-W, Longhurst JC. Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors. J Appl Physiol 106: 1800 -1809, 2009. First published April 9, 2009 doi:10.1152/japplphysiol.91648.2008.-Previous studies have demonstrated that electroacupuncture (EA) attenuates sympathoexcitatory reflex responses by activating a long-loop pathway involving the hypothalamic arcuate nucleus (ARC), midbrain ventrolateral periaqueductal gray (vlPAG), and rostral ventrolateral medulla (rVLM). Neurons in the ARC provide excitatory input to the vlPAG, whereas the vlPAG inhibits neuronal activity in the rVLM. ␥-Aminobutyric acid (GABA) and glutamate (Glu) have been identified in the vlPAG. Endocannabinoids (ECs), acting as atypical neurotransmitters, inhibit the release of both neurotransmitters in the hypothalamus and midbrain through a presynaptic cannabinoid type 1 (CB1) receptor mechanism. The EC system has been observed in the dorsal but not in the vlPAG. Since it is uncertain whether ECs influence GABA and Glu in the vlPAG, the present study tested the hypothesis that EA modulates the release of these neurotransmitters in the vlPAG through a presynaptic CB1 receptor mechanism. We measured the release of GABA and Glu simultaneously by using HPLC to assess samples collected with microdialysis probes inserted unilaterally into the vlPAG of intact anesthetized rats. Twenty-eight min of EA (2 Hz, 2-4 mA, 0.5 ms) at the P5-6 acupoints reduced the release of GABA by 39% during EA and by 44% 15 min after EA. Thirty-five minutes after EA, GABA concentrations returned to pre-EA levels. In contrast, sham EA did not change the vlPAG GABA concentration. Blockade of CB1 receptors with AM251, a selective CB1 receptor antagonist, reversed the EA-modulated changes in GABA concentration, whereas microinjection of vehicle into the vlPAG did not alter EA-modulated GABA changes. In addition, we observed no changes in the vlPAG Glu concentrations during EA, although the baseline concentration of Glu was much higher than that of GABA (3,541 Ϯ 373 vs. 33.8 Ϯ 8.7 nM, Glu vs. GABA). These results suggest that EA modulates the sympathoexcitatory reflex responses by decreasing the release of GABA, but not Glu, in the vlPAG, most likely through a presynaptic CB1 receptor mechanism. somatic afferents; sympathoexcitatory reflex; cannabinoid type 1 receptor; microdialysis ELECTROACUPUNCTURE (EA), a potent alternative to manual acupuncture, has been suggested to be effective in treating certain cardiovascular diseases including hypertension, arrhythmias, and angina pectoris (5, 6, 41). Clinically, EA at the NeiguanJianshi (P5-6) acupoints has been used to treat cardiovascular diseases in Eastern and, more recently, Western countries (5, 21, 41). We and others have demonstrated that EA at P5-6 acupoints overlying the median nerve on the wrist modulate blood pressure elevation evoked by gastric distension (GD) in rats (27) or by gallbladder stimulation in cats (50) through a long-loop neural pathway, extending from the arcuate...

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“…Morphological data show coincidence in localization of cannabinoid and opioid receptors in brain areas connected with pain perception control -PAG, nuclei raphe and nuclei centro-mediales thalami [ 15,16 ]. Known experimental data also support the interaction between the endocannabinoid and the endogenous opioid systems in descending pain control.…”

mentioning

confidence: 76%

“…Literature data showed coincidence in the distribution of opioid and CB1 receptors in CNS [ 15,16 ].…”

mentioning

confidence: 86%

Effects of Tyr-MIF-1 Family of Peptides on Endocannabinoid System after Immobilization Stress

Nocheva¹,

Kochev²,

Bocheva³

2013

Proceeding BAS

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Biochemical, physiological and behavioural changes take place during stress. Various stress models have been reported to induce analgesia. This is a phenomenon referred to as stress-induced analgesia (SIA). Two forms of SIA are commonly distinguished: an opioid-mediated and a non-opioid one.In the last decade special attention has been attributed to the endocannabinoid system (ECS) as a component of non-opioid SIA.The Tyr-MIF-1 peptides proved to have opioid-like as well as anti-opioid effects.It has been shown that the endogenous opioid and the endocannabinoid systems have been involved in stress-induced analgesia.We found no literature data about the effects of Tyr-MIF-1 neuropeptides on the endocannabinoid system after stress.The aim of the study was to investigate the effects on nociception of Tyr-MIF-1 peptides (MIF-1, Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1) on the endocannabinoid system after immobilization stress.Anandamide (CB1 agonist) and AM251 (CB1 antagonist) were used. Nociception was measured in male Wistar rats by paw-pressure and hot-plate tests. All drugs were injected intraperitoneally.The results showed that anandamide and AM251 were involved in the analgesic effects of Tyr-MIF-1 peptides after immobilization SIA. The effects are probably due to different interaction between Tyr-MIF-1 receptors and endocannabinoid ones and the different involvement of the opioid and the antiopioid component in immobilization stress.

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CB1-cannabinoid and μ-opioid receptor co-localization on postsynaptic target in the rat dorsal horn

Cited by 149 publications

References 22 publications

Adenosine A2a blockade prevents synergy between μ-opiate and cannabinoid CB1 receptors and eliminates heroin-seeking behavior in addicted rats

Adenosine A2a blockade prevents synergy between μ-opiate and cannabinoid CB1 receptors and eliminates heroin-seeking behavior in addicted rats

Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB₁ receptors

Effects of Tyr-MIF-1 Family of Peptides on Endocannabinoid System after Immobilization Stress

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