Functional role of the endocannabinoid system in emotional homeostasis]

[Sequoiacrone]

1: Rev Neurol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Rev%20Neuro l.%27%29;) 2009 Jan 1-15;48(1):20-6.
[Functional role of the endocannabinoid system in emotional homeostasis]

[Article in Spanish]


Marco EM (http://www.oregongreenfree.net/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Marco%20EM%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Viveros MP (http://www.oregongreenfree.net/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Viveros%20MP%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Departamento de Fisiología, Universidad Complutense, Madrid, España.
INTRODUCTION AND DEVELOPMENT: Cannabis and derivatives induce complex effects on anxiety in humans and experimental animals. At low doses, cannabinoid agonists seem to exert anxiolytic actions, while at high doses anxiety and panic estates are often reported. Diverse animal models confirm this particular biphasic profile; however, the underlying neurobiological mechanisms have not been completely elucidated. The anxiogenic-like behavioral phenotype observed following both pharmacological and genetic blockade of cannabinoid CB1 receptors, together with the abundant expression of cannabinoid receptors within brain areas particularly involved in emotional control, such as amygdala, hippocampus and cortex, are among the numerous evidences that account for the participation of the endocannabinoid system in the regulation of anxiety states. Moreover, blockade of endogenous cannabinoid ligands deactivation has been reported to induce anxiolytic-like responses. CONCLUSIONS: Taken together, present data reinforce the involvement of the endocannabinoid system in the control of emotional homeostasis and further suggest the pharmacological manipulation of the endocannabinoid system as a potential therapeutic tool in the management of anxiety-related disorders.
PMID: 19145562 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/19145562

[Sequoiacrone]

1: Crit Rev Neurobiol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Crit%20Rev% 20Neurobiol.%27%29;) 1999;13(3):243-81.

Behavioral effects of cannabinoid agents in animals.

Chaperon F (http://www.oregongreenfree.net/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Chaperon%20F%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Thiébot MH (http://www.oregongreenfree.net/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Thi%C3%A9bot%20MH%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
INSERM U.288 and Department of Pharmacology, Faculty of Medicine Pitié-Salpêtrière, Paris, France.
Two subtypes of cannabinoid receptors have been identified to date, the CB1 receptor, essentially located in the CNS, but also in peripheral tissues, and the CB2 receptor, found only at the periphery. The identification of delta9-tetrahydrocannabinol (delta9-THC) as the major active component of marijuana (Cannabis sativa), the recent emergence of potent synthetic ligands and the identification of anandamide and sn-2 arachidonylglycerol as putative endogenous ligands for cannabinoid receptors in the brain, have contributed to advancing cannabinoid pharmacology and approaching the neurobiological mechanisms involved in physiological and behavioral effects of cannabinoids. Most of the agonists exhibit nonselective affinity for CB1/CB2 receptors, and delta9-THC and anandamide probably act as partial agonists. Some recently synthesized molecules are highly selective for CB2 receptors, whereas selective agonists for the CB1 receptors are not yet available. A small number of antagonists exist that display a high selectivity for either CB1 or CB2 receptors. Cannabinomimetics produce complex pharmacological and behavioral effects that probably involve numerous neuronal substrates. Interactions with dopamine, acetylcholine, opiate, and GABAergic systems have been demonstrated in several brain structures. In animals, cannabinoid agonists such as delta9-THC, WIN 55,212-2, and CP 55,940 produce a characteristic combination of four symptoms, hypothermia, analgesia, hypoactivity, and catalepsy. They are reversed by the selective CB1 receptor antagonist, SR 141716, providing good evidence for the involvement of CB1-related mechanisms. Anandamide exhibits several differences, compared with other agonists. In particular, hypothermia, analgesia, and catalepsy induced by this endogenous ligand are not reversed by SR 141716. Cannabinoid-related processes seem also involved in cognition, memory, anxiety, control of appetite, emesis, inflammatory, and immune responses. Agonists may induce biphasic effects, for example, hyperactivity at low doses and severe motor deficits at larger doses. Intriguingly, although cannabis is widely used as recreational drug in humans, only a few studies revealed an appetitive potential of cannabimimetics in animals, and evidence for aversive effects of delta9-THC, WIN 55,212-2, and CP 55,940 is more readily obtained in a variety of tests. The selective blockade of CB1 receptors by SR 141716 impaired the perception of the appetitive value of positive reinforcers (food, cocaine, morphine) and reduced the motivation for sucrose, beer and alcohol consumption, indicating that positive incentive and/or motivational processes could be under a permissive control of CB1-related mechanisms. There is little evidence that cannabinoid systems are activated under basal conditions. However, by using SR 141716 as a tool, a tonic involvement of a CB1-mediated cannabinoid link has been demonstrated, notably in animals suffering from chronic pain, faced with anxiogenic stimuli or highly motivational reinforcers. Some effects of SR 141716 also suggest that CB1-related mechanisms exert a tonic control on cognitive processes. Extensive basic research is still needed to elucidate the roles of cannabinoid systems, both in the brain and at the periphery, in normal physiology and in diseases. Additional compounds, such as selective CB1 receptor agonists, ligands that do not cross the blood brain barrier, drugs interfering with synthesis, degradation or uptake of endogenous ligand(s) of CB receptors, are especially needed to understand when and how cannabinoid systems are activated. In turn, new therapeutic strategies would likely to emerge.
PMID: 10803637 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/10803637?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedreviews&logdbfrom=pubmed

[Sequoiacrone]

Endocannabinoid system and stress and anxiety responses.

Viveros MP (http://www.oregongreenfree.net/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Viveros%20MP%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Marco EM (http://www.oregongreenfree.net/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Marco%20EM%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), File SE (http://www.oregongreenfree.net/sites/entrez?Db=pubmed&Cmd=Search&Term=%22File%20SE%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Departmento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, 28040 Madrid, Spain. pazviver@bio.ucm.es
Cannabinoid agonists induce complex and often contradictory effects on anxiety in humans and experimental animals. The data from animal tests provide evidence of dose-dependent bidirectional modulation of anxiety by the cannabinoid system and the importance of environmental context. The mechanisms mediating the effects of cannabinoids on anxiety-related responses appear to involve CB1 and non-CB1 cannabinoid receptors. In addition, the CRH, GABA(A), cholecystokinin, opioid and serotonergic systems have also been implicated. Brain regions such as the amygdala, hippocampus and cortex, directly involved in the regulation of emotional behavior, contain high densities of CB1 receptors. Mutant mice lacking CB1 receptors show anxiogenic-like and depressive-like phenotypes in several tests, as well as profound alterations in their adrenocortical activity. Pharmacological blockade of CB1 receptors induces anxiety in rats, and inhibition of anandamide metabolism produces anxiolytic-like effects. Thus, the endocannabinoid system appears to play a pivotal role in the regulation of emotional states and may constitute a novel pharmacological target for anti-anxiety therapy.
PMID: 15927244 [PubMed - indexed for MEDLINE]
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