378 Brain Research, 452 (1988) 378-380 Elsevier BRE 22944 Effects of systemic L-tyrosine on dopamine release from rat corpus striatum and nucleus accumbens Matthew J. During, Ian N. Acworth and Richard J. Wurtman Laboratory of Neuroendocrine Regulation, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 (U.S.A.) (Accepted 8 March 1988) Key words: Brain dialysis; Dopamine release; Tyrosine; Striatum; Nucleus accumbens Intracerebral dialysis was used to monitor extracellular fluid from rat striatum and nucleus accumbens followingthe intraperitoneal administration of tyrosine. Dopamine concentrations in dialysates from both the striatum and the nucleus accumbens increased signifi- cantly in response to the tyrosine. The magnitude of the tyrosine effect was greater in the nucleus accumbens than in the striatum. Hence, mesolimbicdopaminergicneurons may be especially responsive to precursor availability. Acute administration of the large neutral amino acid L-tyrosine can increase brain dopamine 5"14, and treatments which raise or lower rat brain tyrosine concentrations can cause parallel changes in the rate at which L-dihydroxyphenylalanine (L-DOPA) accu- mulates (after aromatic amino acid decarboxylase in- hibition) 2'6'23. The abilitity of tyrosine supplementa- tion to enhance catecholamine synthesis has been es- tablished using a variety of experimental manipula- tions in which the catecholaminergic neurons are rap- idly firing 11'16 and their tyrosine hydroxylase conse- quently is 'activated '18 (e.g. in the prefrontal cortex 19 where the dopaminergic input physiologically ex- hibits a high firing rate and bursting activity3). It has been postulated that such precursor-induced in- creases in dopamine synthesis are coupled to in- creases in release12't6; however, direct in vivo evi- dence for increased release is lacking. Using an intracerebral dialysis technique, we have investigated the effect of tyrosine administration on dopamine release, in vivo, in anesthetized but other- wise-untreated rats, and have compared the re- sponses of the dopaminergic neurons terminating in the corpus striatum with those terminating in the nu- cleus accumbens. Brain microdialysis is becoming in- creasingly established as a useful method for repeat- ed sampling of the extracellular fluid of discrete brain regions in vivo 9'10'17'20-22'24. We used a Carnegie Me- dicin (Solna, Sweden) brain dialysis system coupled to a liquid chromatograph with electrochemical de- tection to monitor levels of dopamine and its metabo- lites in brain extracellular fluid. The dialysis system consisted of a concentric probe (supplied by Carne- gie Medicin: outer diameter 0.5 mm, molecular weight cut off, 5,000 Da; membrane length 4 mm (striatum) or 2 mm (nucleus accumbens)) perfused by a CMA 100 microperfusion pump delivering an ar- tificial cerebrospinal fluid (CSF composition (mM): Na + 147; K + 3.5; Ca 2+ 1.0; Mg2+1.2; C1- 129; phos- phate 1; HCO 3- 25; pH 7.4) at a flow rate of 1.5 ktl/ min. Dialysis probes were calibrated in vivo prior to implantation using standard solutions of known con- centration (dopamine and DOPAC, 100 nM, HVA 300 nM). Male Sprague Dawley rats, weighing 300-400 g, were anesthetized with chloralose/urethane (50/500 mg kg -1 i.p.) and placed in a David Kopf stereotaxic frame. The skull was exposed and a hole drilled above either the right central striatum or the right nu- cleus accumbens. The dialysis probe was implanted Correspondence: R.J. Wurtman, E25-604, Massachusetts Institute of Technology,Cambridge, MA 02139, U.S.A.