%0 Journal Article
%T Laurate Biosensors Image Brain Neurotransmitters In Vivo: Can an Antihypertensive Medication Alter Psychostimulant Behavior?
%A Patricia A. Broderick
%A Helen Ho
%A Karyn Wat
%A Vivek Murthy
%J Sensors
%D 2008
%I MDPI AG
%R 10.3390/s8074033
%X 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/2C receptors, 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.
%K anxiety
%K brain
%K caffeine
%K cocaine
%K dopamine
%K electrochemistry
%K G-protein receptor complexes (GPRC)
%K homovanillic acid
%K hypertension
%K ketanserin
%K L-tryptophan
%K mesolimbic
%K motor tracts
%K neuromolecular imaging
%K nucleus accumbens
%K open-field behaviors
%K psychostimulants
%K serotonin
%K ventral tegmental area.
%U http://www.mdpi.com/1424-8220/8/7/4033