title: Laurate Biosensors Image Brain Neurotransmitters In Vivo: Can an Antihypertensive Medication Alter Psychostimulant Behavior?
abstract: Neuromolecular Imaging (NMI) with novel biosensors enables the selective detection of neurotransmitters in vivo within seconds, on line and in real time. Biosensors remain in place for continuing studies over a period of months. This biotechnological advance is based on conventional electrochemistry; the biosensors detect neurotransmitters by electron transfer. Simply stated, biosensors adsorb electrons from each neurotransmitter at specific oxidation potentials; the current derived from electron transfer is proportional to neurotransmitter concentration. Selective electron transfer properties of these biosensors permit the imaging of neurotransmitters, metabolites and precursors. The novel BRODERICK PROBE®biosensors we have developed, differ in formulation and detection capabilities from biosensors/electrodes used in conventional electrochemistry/ voltammetry. In these studies, NMI, specifically, the BRODERICK PROBE®laurate biosensor images neurotransmitter signals within mesolimbic neuronal terminals, nucleus accumbens (NAc); dopamine (DA), serotonin (5-HT), homovanillic acid (HVA) and Ltryptophan (L-TP) are selectively imaged. Simultaneously, we use infrared photobeams to monitor open-field movement behaviors on line with NMI in the same animal subjects. The goals are to investigate integrated neurochemical and behavioral effects of cocaine and caffeine alone and co-administered and further, to use ketanserin to decipher receptor profiles for these psychostimulants, alone and co-administered. The rationale for selecting this medication is: ketanserin (a) is an antihypertensive and cocaine and caffeine produce hypertension and (b) acts at 5-HT2A/2Creceptors, prevalent in NAc and implicated in hypertension and cocaine addiction. Key findings are: (a) the moderate dose of caffeine simultaneously potentiates cocaine's neurochemical and behavioral responses. (b) ketanserin simultaneously inhibits cocaine-increased DA and 5-HT release in NAc and open-field behaviors and (c) ketanserin inhibits 5-HT release in NAc and open-field behaviors produced by caffeine, but, surprisingly, acts to increase DA release in NAc. Importantly, the latter effect may be a possible adverse effect of the moderate dose of caffeine in hypertensive patients. Thus, an antihypertensive medication is shown here to play a role in inhibiting brain reward possibly via antihypertensive mechanisms at DA and 5-HT receptor subtypes within DA motor neurons. An explanatory note for the results obtained, is the role likely played by the G Protein Receptor Complex (GPRC) family of proteins. Empirical evidence shows that GPRC dimers, heteromers and heterotrimers may cause cross-talk between distinct signalling cascade pathways in the actions of cocaine and caffeine. Ligand-directed functional selectivity, particularly for ketanserin, in addition to GPRCs, may also cause differential responses. The results promise new therapeutic strategies for drug addiction, brain reward and cardiovascular medicine.
authors.affiliation: Dept.of Physiology and Pharmacology, The City University of New York (CUNY), USA. broderick@med.cuny.edu.|Doctoral Program, Dept. Biology, Dept. Psychology, CUNY Graduate School, NY, NY, USA. broderick@med.cuny.edu.|Dept.of Neurology, NYU School of Medicine, NYU Comprehensive Epilepsy Center, NY,NY,USA. broderick@med.cuny.edu.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Broderick
authors.affiliation: Dept.of Physiology and Pharmacology, The City University of New York (CUNY), USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Ho
authors.affiliation: Dept.of Physiology and Pharmacology, The City University of New York (CUNY), USA.
authors.forename: Karyn
authors.initials: K
authors.lastname: Wat
authors.affiliation: Dept.of Physiology and Pharmacology, The City University of New York (CUNY), USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Murthy
keywords: G-protein receptor complexes (GPRC); L-tryptophan; anxiety; brain; caffeine; cocaine; dopamine; electrochemistry; homovanillic acid; hypertension; ketanserin; mesolimbic; motor tracts; neuromolecular imaging; nucleus accumbens; open-field behaviors; psychostimulants; serotonin; ventral tegmental area.