Brain Research, 500 (1989) 241-246 241 Elsevier BRES 14894 Measurement of 3-methoxytyramine by in vivo voltammetry: evidence for differences in central dopamine function in BALB/c and CBA mice F. Crespi 1"4, K.F. Martin 2, D.J. Heal 2, C.A. Marsden 1, W.R. Buckett 2 and M.K. Sanghera 3 1Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, (U. K.), -'Research Department, The Boots Company PLC, Nottingham (U.K.), ~Department of Psychiatry, UT Southwestern Medical Centre, Dallas, TX (U.S.A.) and 41stituto di Ricerche Farmacologiche Mario Negri, Milano (ltaly) (Accepted 21 March 1989) Key words: In vivo voltammetry; Mouse; 3-Methoxytyramine, Dopamine Differential pulse voltammetry (DPV) combined with carbon fibre electrodes allows selective detection of electroactive dopamine and serotonin metabolites in vivo. While usually employed in rats, we have now applied this in vivo technique in two inbred strains of mice: BALB/c and CBA. Three distinct oxidation peaks were recorded in vivo in the striatum of either BALB/c or CBA mice with a small shoulder occurring after the third peak at approximately +400 inV. Pargyline (150 mg/kg i.p.) potentiated this voltammetric shoulder into an easily measurable peak (Peak 4). In addition, Peak 4 was 2-3 times larger in BALB/c than in CBA mice. Homovanillic acid (HVA) and 3-methoxytyramine (3-MT), both catabolites of dopamine, oxidised at approximately +400 mV in vitro. Brain tissue levels of HVA and 3-MT, measured by high-performance liquid chromatography (HPLC) with electrochemical detection, demonstrated that pargyline treatment reduced striatal HVA, but increased 3-MT. These results support the view that Peak 4 recorded in the striatum of pargyline-treated mice in vivo is due to the oxidation of extracellular 3-MT. Thus, Peak 4 may be a useful index of dopamine release in situations where dopamine itself cannot be detected. Local infusion of KCI (2 ul, 0.1 M) further increased the size of Peak 4 in the striatum of both BALB/c and CBA mice. However, the increase was approx. 3 times greater in BALB/c mice, supporting previous evidence of greater dopaminergic function of BALB/c compared with CBA mice. In addition these two inbred strains of mice provide model systems for investigating the comparative functional roles of nigrostriatal pathways. INTRODUCTION When combined with carbon-based electrodes, voltammetry can be used for detecting the oxidation of electroactive compounds in vivo 1'~6. Bebavioural and/or pharmacological experiments employing drugs acting on catechol or 5-hydroxyindole metab- olism, have amply demonstrated the specificity and sensitivity of electrochemically pretreated carbon fibre electrodes (biosensors) used in conjunction with differential pulse voltammetry (DPV) for mon- itoring amine metabolites in specific brain areas of rat 3-5'13. The method has advantages over sampling techniques (e.g. intracerebral dialysis 1~) both in the speed and frequency of measurement. The small size of the biosensor (12 ktm in diameter) gives superior regional localisation and produces less trauma of the nervous tissue. Furthermore, the detection of elec- troactive compounds occurs in situ and at real time. We have previously reported on an improved elec- trical pretreatment of the 12 ~m carbon fibre electrode, so that it is now possible to monitor simultaneously the oxidation of extracellular ascor- bic acid (AA; peak 1 at -50 mV), 3,4-dihydroxy- phenylacetic acid (DOPAC; Peak 2 at +100 mV) and a mixture of 70% 5-hydroxyindoleacetic acid Correspondence." F. Crespi, Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham NG7 2UH, U.K. (/006-8993/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)