Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist

Psychopharmacology
Sherrica TaiTorbjörn U C Järbe

Abstract

Previous reports shows rimonabant's inverse properties may be a limiting factor for treating cannabinoid dependence. To overcome this limitation, neutral antagonists were developed, to address mechanisms by which an inverse agonist and neutral antagonist elicit withdrawal. The objective of this study is to introduce an animal model to study cannabinoid dependence by incorporating traditional methodologies and profiling novel cannabinoid ligands with distinct pharmacological properties/modes of action by evaluating their pharmacological effects on CB1-receptor (CB1R) related physiological/behavioral endpoints. The cannabinergic AM2389 was acutely characterized in the tetrad (locomotor activity, analgesia, inverted screen/catalepsy bar test, and temperature), with some comparisons made to Δ(9)-tetrahydrocannabinol (THC). Tolerance was measured in mice repeatedly administered AM2389. Antagonist-precipitated withdrawal was characterized in cannabinoid-adapted mice induced by either centrally acting antagonists, rimonabant and AM4113, or an antagonist with limited brain penetration, AM6545. In the tetrad, AM2389 was more potent and longer acting than THC, suggesting a novel approach for inducing dependence. Repeated administration o...Continue Reading

References

Jan 1, 1976·Annals of the New York Academy of Sciences·R T JonesJ Bachman
Mar 1, 1977·Pharmacology, Biochemistry, and Behavior·L L CoughenourR B Parker
Aug 1, 1981·Journal of Clinical Pharmacology·R T JonesR I Herning
Apr 16, 1998·Pain·Jennelle Durnett RichardsonKenneth M Hargreaves
May 10, 2000·Critical Reviews in Neurobiology·F Chaperon, M H Thiébot
Apr 3, 2001·European Journal of Pharmacology·M D AcetoB B Martin
Jun 23, 2001·Pharmacology, Biochemistry, and Behavior·A H LichtmanB R Martin
Jun 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Aron H LichtmanBenjamin F Cravatt
Nov 29, 2002·Psychopharmacology·Carl L HartMarian W Fischman
Mar 19, 2003·Journal of Neurochemistry·José M OlivaJorge Manzanares
Jul 2, 2004·The Journal of Pharmacology and Experimental Therapeutics·Aron H LichtmanBenjamin F Cravatt
Jul 20, 2005·Mini Reviews in Medicinal Chemistry·Ganesh A ThakurAlexandros Makriyannis
Apr 7, 2006·Handbook of Experimental Pharmacology·A H Lichtman, B R Martin
Aug 25, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yasushi Kishimoto, Masanobu Kano
Aug 29, 2006·Pharmacology, Biochemistry, and Behavior·David M WilsonAron H Lichtman
Jun 22, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Kelly S SinkJohn D Salamone
Oct 26, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Adam P ChambersKeith A Sharkey
Jul 29, 2010·The Journal of Clinical Investigation·Joseph TamGeorge Kunos
Oct 17, 2012·Molecular Psychiatry·F J MeyeR A H Adan
Oct 9, 2013·European Journal of Pharmacology·Girish R ChopdaCarol A Paronis
Jun 1, 2014·Current Addiction Reports·Sherrica Tai, William E Fantegrossi

❮ Previous
Next ❯

Citations

Aug 25, 2016·Drug Discovery Today·Oier Aizpurua-OlaizolaAresatz Usobiaga
May 7, 2016·Journal of Basic and Clinical Physiology and Pharmacology·Travis W GrimAron H Lichtman
Oct 27, 2021·Endocrine Reviews·Angeliki M AngelidiChristos S Mantzoros

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.