Chronic baclofen desensitizes GABA(B)-mediated G-protein activation and stimulates phosphorylation of kinases in mesocorticolimbic rat brain

Neuropharmacology
Bradley M T KeeganAllyn C Howlett

Abstract

The GABAB receptor is a therapeutic target for CNS and neuropathic disorders; however, few preclinical studies have explored effects of chronic stimulation. This study evaluated acute and chronic baclofen treatments on GABAB-activated G-proteins and signaling protein phosphorylation as indicators of GABAB signaling capacity. Brain sections from rats acutely administered baclofen (5 mg/kg, i.p.) showed no significant differences from controls in GABAB-stimulated GTPγS binding in any brain region, but displayed significantly greater phosphorylation/activation of focal adhesion kinase (pFAK(Tyr397)) in mesocorticolimbic regions (caudate putamen, cortex, hippocampus, thalamus) and elevated phosphorylated/activated glycogen synthase kinase 3-β (pGSK3β(Tyr216)) in the prefrontal cortex, cerebral cortex, caudate putamen, nucleus accumbens, thalamus, septum, and globus pallidus. In rats administered chronic baclofen (5 mg/kg, t.i.d. for five days), GABAB-stimulated GTPγS binding was significantly diminished in the prefrontal cortex, septum, amygdala, and parabrachial nucleus compared to controls. This effect was specific to GABAB receptors: there was no effect of chronic baclofen treatment on adenosine A1-stimulated GTPγS binding in an...Continue Reading

References

Jan 15, 1978·European Journal of Pharmacology·H K Proudfit, R A Levy
Mar 1, 1989·The American Journal of Psychiatry·M F BreslowD G Hope
Jan 1, 1989·European Journal of Clinical Pharmacology·E W WuisE Van der Kleijn
Jul 1, 1984·Journal of Toxicology. Clinical Toxicology·P AndersonC G Swahn
Aug 1, 1995·Proceedings of the National Academy of Sciences of the United States of America·L J SimS R Childers
Nov 30, 1993·European Journal of Pharmacology·M MalcangioN G Bowery
Nov 21, 1996·Biochemical and Biophysical Research Communications·M B CalalbS K Hanks
Aug 10, 1999·The Journal of Comparative Neurology·S BischoffB Bettler
Apr 5, 2002·Clinical Neurology and Neurosurgery·Jørgen Feldbaek NielsenJens Just Christensen
Dec 19, 2002·Molecular Pharmacology·Trudy A Kohout, Robert J Lefkowitz
Mar 18, 2003·Journal of Cell Science·J Thomas Parsons
Mar 22, 2003·The Journal of Pharmacology and Experimental Therapeutics·S A SandsS J Enna
Oct 31, 2003·Molecular and Cellular Biology·Lee Ann CooperJun-Lin Guan
Mar 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jean-Martin BeaulieuMarc G Caron
Oct 16, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Rita A FuchsRonald E See
Jan 13, 2005·The Journal of Pharmacology and Experimental Therapeutics·Kerry A O'ConnorSteven R Childers
Feb 1, 2005·European Journal of Pharmacology·David A KaranianBen A Bahr
May 5, 2005·The European Journal of Neuroscience·Prathiba Jayaram, Jeffery D Steketee
Dec 16, 2005·The AAPS Journal·Per SvenningssonPaul Greengard
Dec 20, 2005·Current Opinion in Pharmacology·Norman G Bowery
Feb 24, 2006·The American Journal of Medicine·Giovanni AddoloratoGiovanni Gasbarrini
Jun 13, 2006·Cellular and Molecular Neurobiology·Yi PanHaohua Qian
Nov 15, 2006·Current Drug Targets·Richard S Jope, Myoung-Sun Roh

❮ Previous
Next ❯

Citations

May 23, 2018·Brain and Behavior·Shimriet ZeidlerRob Willemsen
Nov 22, 2018·Frontiers in Psychiatry·Renaud de Beaurepaire
Jun 27, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Magali ChartierBruno Mégarbane

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amygdala: Sensory Processes

Amygdalae, nuclei clusters located in the temporal lobe of the brain, play a role in memory, emotional responses, and decision-making. Here is the latest research on sensory processes in the amygdala.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Bipolar Disorder

Bipolar disorder is characterized by manic and/or depressive episodes and associated with uncommon shifts in mood, activity levels, and energy. Discover the latest research this illness here.

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.