Thus, NMI provides a close cause and effect relationship between brain and behavior. Current technologies, e.g., microdialysis, are limited because microdialysis devices can traumatize brain tissue (1).We used NMI, based on an electrochemical method of analysis, because NMI provides advantages over spectroscopic or chromatographic methods. For example, NMI (a) enhances the specificity, selectivity, simplicity and sensitivity of its spectroscopic and chromatographic counterparts, (b) does not need pre-/post-assay functional group derivatives and (c) selectively detects neurotransmitters within a complex living matrix in vivo.The precise focus of our studies in brain is the mesolimbic pathway in the freely moving (unrestrained) and behaving animal in vivo.

Figure 1 depicts schematically the mesolimbic neuronal circuit in brain. We collaborated with Dr. Clyde Phelix, San Antonio, Texas, to perform immunocytochemical studies that show a significant overlap in the presence of DA and 5-HT in DA axons in NAc at the site of the BRODERICK PROBE? biosensor (2). Figure 2 shows the immunocytochemistry results. It is important to note here that serotonergic cells in 5-HT cell bodies in dorsal raphe project axons to NAc; these axons play a critical role in the DA mesolimbic pathway to neuromodulate movement behavior (3).Figure 1.Human (left) and murine brain (right) depicting mesolimbic and mesocortical DA pathways which originate in VTA and send ascending projections to NAc and Prefrontal Cortex (PFC).

Feelings of reward as well as aversion are derived herein. VTA sends descending .

..Figure Drug_discovery 2.Immunocytographs of DA and 5-HT in NAc (ventrolateral (vl)) of Sprague Dawley laboratory rats. Dark field photomicrographs show the distribution of (A) DA neurons, stained with tyrosine hydroxylase; two high density patterns of DA are apparent in the …The aims are to use NMI, BRODERICK PROBE? laurate biosensors and infrared photobeams to (a) study in vivo integrated neurochemistry and behavior produced by cocaine and caffeine alone and co-administered and (b) study the effects of the antihypertensive medication, ketanserin, on cocaine and caffeine responses alone and co-administered.

Cocaine is known to be a reinforcer of psychostimulant behavior (4). Cocaine increases Brefeldin_A DA reuptake inhibition and DA release at the synapse in mesolimbic and nigrostriatal brain reward centers, thereby inducing a feeling of ��joie de vivre��. Cocaine enhances brain reward by pharmacologic sensitization, i.e., repeated use causes enhanced reward in part, via adenosine inhibitors (5,6). Nonetheless, cocaine produces neuroadaptive withdrawal symptoms and hypertension (4,7).