Functional expression of brain neuronal CB2 cannabinoid receptors are involved in the effects of drugs of abuse and in depression.

Major depression and addiction are mental health problems associated with stressful events in life with high relapse and recurrence even after treatment. Many laboratories were not able to detect the presence of CB2 cannabinoid receptors (CB2-Rs) in healthy brains, but CB2-R expression has been demonstrated in rat microglial cells and other brain-associated cells during inflammation. Thus, neuronal expression of CB2-Rs has been ambiguous and controversial, and its role in depression and substance abuse is unknown.

Disruption of agonist and ligand activity in an AMPA glutamate receptor splice-variable domain deletion mutant.

The mechanisms by which agonists and other ligands bind ligand-gated ion channels are important determinants of function in neurotransmitter receptors. The partial agonist, kainic acid (KA) activates a less desensitized, and more robust AMPA receptor (AMPAR) current than full agonists, glutamate or AMPA. Cyclothiazide (CTZ), the allosteric modulator of AMPARs, potentiates receptor currents by inhibiting receptor desensitization resulting from agonist activation.

Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.

Background: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs) in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown.

Molecular neurobiological methods in marijuana-cannabinoid research.

Recent aggregation of evidence for the roles of endogenous agonist and receptor systems that are mimicked or activated by cannabanoid ligands has provided a focus for work that has elucidated details of some of the multiple physiological roles and pharmacological functions that these systems play in brain and peripheral tissues. This chapter reviews some of the approaches to improved elucidation of these systems, with special focus on the human genes that encode cannabanoid receptors and the variants in these receptors that appear likely to contribute to human addiction vulnerabilities.

Ethanol sensitivity of recombinant homomeric and heteromeric AMPA receptor subunits expressed in Xenopus oocytes.

Background: Ethanol is known to acutely inhibit AMPA receptor function, and sensitivity of AMPA receptors to ethanol is dependent on subunit composition in vivo and in vitro. A commonly used in vitro expression system for studying recombinant receptor subunits is the Xenopus laevis oocyte and two-electrode voltage-clamp electrophysiological recording. To date, ethanol sensitivity of injected receptor subunit complementary RNA (cRNA) has not been shown to be correlated with the actual expression of receptor subunits in oocytes.

Cellular migration in the postnatal rat cerebellar cortex: confocal-infrared microscopy and the rapid Golgi method.

Confocal laser microscopy of DiI-labeled slices of postnatal rat cerebellum (postnatal Day 4-10; P4-10) was compared to infrared microscopy and the rapid Golgi method (P0-14) to investigate postnatal migration of granule neurons. Vertical migration of the granule neurons occurred already at birth (P0). Surprisingly, mossy fibers often reached the external granule cell layer and were in close contact with the external granule cells.

Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation.

The mapping of the human genetic code will enable us to identify potential gene products involved in human addictions and diseases that have hereditary components. Thus, large-scale, parallel gene-expression studies, made possible by advances in microarray technologies, have shown insights into the connection between specific genes, or sets of genes, and human diseases. The compulsive use of addictive substances despite adverse consequences continues to affect society, and the science underlying these addictions in general is intensively studied.