NEUROCHEMISTRY NEUROREPORT 0959-4965 & Lippincott Williams & Wilkins Vol 12 No 11 8 August 2001 2549 Sub-second changes in accumbal dopamine during sexual behavior in male rats Donita L. Robinson, Paul E. M. Phillips, Evgeny A. Budygin, B. Jill Trafton, Paul A. Garris 1 and R. Mark Wightman CA Department of Chemistry and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599; 1 Department of Biological Sciences, Illinois State University, Normal, IL 61790, USA CA Corresponding Author Received 19 April 2001; accepted 5 June 2001 Transient (200±900 ms), high concentrations (200±500 nM) of dopamine, measured using fast-scan cyclic voltammetry, oc- curred in the nucleus accumbens core of male rats at the presentation of a receptive female. Additional dopamine signals were observed during subsequent approach behavior. Back- ground-subtracted cyclic voltammograms of the naturally- evoked signals matched those of electrically-evoked dopamine measured at the same recording sites. Administration of nomifensine ampli®ed natural and evoked dopamine release, and increased the frequency of detectable signals. While gradual changes in dopamine concentration during sexual behavior have been well established, these ®ndings dramatically improve the time resolution. The observed dopamine transi- ents, probably resulting from neuronal burst ®ring, represent the ®rst direct correlation of dopamine with sexual behavior on a sub-second time scale. NeuroReport 12:2549±2552 & 2001 Lippincott Williams & Wilkins. Key words: Burst ®ring; Dopamine; Fast-scan cyclic voltammetry; Nucleus accumbens; Rat; Reward; Sex behavior INTRODUCTION Dopamine (DA) neurons ®re in tonic and phasic patterns [1,2]. Phasic, or burst ®ring, appears to be coordinated in a large proportion of DA neurons by sensory input [3]. For example, Mirenowicz and Schultz [4] found that 78±85% of DA neurons ®red in response to the presentation of a primary reward. Moreover, burst ®ring ef®ciently produces DA release at the terminal region [5,6]. Fast-scan cyclic voltammetry is ideally suited for measuring transient, sub- second changes in DA release that would be expected during burst ®ring in the freely moving rat. However, to date only one study [7] has looked at such changes, in which DA release in the nucleus accumbens (NA) shell, but not the core or caudate, accompanied entry into a novel environment. A large body of literature has con®rmed that DA plays an important role in sexual behavior [8]. In general, nigrostriatal DA is necessary for sensorimotor coordina- tion, hypothalamic DA is necessary for consummatory aspects, and mesolimbic dopamine is necessary for appeti- tive aspects, although there is some overlap among sys- tems. Increased extracellular DA concentrations have been measured in these brain regions during male sexual behav- ior using in vivo microdialysis and slower-scan voltammet- ric techniques [e.g. 9±12]. However, as these experiments monitored changes on a time scale of minutes, it is unclear whether DA concentrations increased gradually or quickly, or whether they were associated with general or speci®c cues and behaviors. Fast-scan cyclic voltammetry provides the unprecedented opportunity to search for rapid changes in DA that may be associated with individual cues. While sampling in microdialysis may involve collection of a value every 300 s [13], the fast-scan technique acquires a value every 0.1 s, a 3000-fold improvement in temporal resolu- tion. The purpose of the present study was to measure changes in extracellular DA release in the NA core of a male rat at the presentation of a sexually receptive female and during subsequent copulatory behavior. We tested the hypothesis that transient changes in DA concentrations in the NA core correspond to salient cues and appetitive aspects of sexual behavior in male rats. MATERIALS AND METHODS Animals: Experiments were performed in four sexually naive male Sprague±Dawley rats (300±400 g; Charles Riv- er, Raleigh, NC). Male rats were singly housed and stimulus females were multiply housed. All rats had free access to food and water and were maintained on a 12:12 h light:dark cycle (lights on at midnight). Estrous cycles of the females were monitored daily by vaginal lavage and inspection of cell morphology. Females were determined to be sexually receptive at the start of the dark cycle at proestrus, when lordosis was observed at a stimulus to the back. All experimental procedures were approved by the Institutional Animal Care and Use Committee at the University of North Carolina. Surgical preparation: Rats were anesthetized with keta- mine (80 mg/kg) and xylazine (12 mg/kg) and placed in a