Physiology ~4 Behavior. Vol. 59, No. 2, pp. 361-367. 19% Copyright $, I996 Elsevier Science Inc. Prmkd in the USA. All rights mened m-9384/96 $15.00 t 00 0031-9384(95)02010-S Effect of Exposure to Novelty on Brain Monoamines in C57BL/6 and DBA/2 Mice BYRON C. JONES,’ XU HOU AND MELLON1 N. COOK Program in Biobehavioral Health, The Pennsylvania State University, University Park, PA 16802-6508 USA Received 15 December 1993 JONES, B. C., X. HOU AND M. N. COOK. EfPect of exposure to novelty on brain monoamines in C57BL/6 and DBA /2 mice. PHYSIOL BEHAV 59(2) 361-367, 1996.-Male and female mice from two inbred strains, C57BL/6 (B6) and DBA/2 (D2), were exposed to a novel environment (vs. undisturbed control) for 10 min. Immediately after this treatment, the animals were sacrificed by cervical dislocation, and the brains were removed and dissected into ventral midbrain &MB), caudate-putamen (CP), nucleus accumbens (NA), and medial prefrontal cortex (FC). Analyses of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC), homovanillic acid @VA) and serotonin (S-HT) and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) were made by high-performance liquid chromatography. Utilization of the parent amines was estimated by the ratios, DOPAC/DA, HVA/DA, and S-HIAA/S-HT. Novelty increased DOPAC levels in NA of both strains of mice and in CP of D2 males; however, it did not induce significant changes in DA, or 5-HT levels or utilization of the latter. The results did, however, reveal large strain differences in DA and its metabolites. The data suggest that genetically based neurophysiological and neurochemical differences exist in dopaminergic and serotonergic systems in mice, and that the DA systems in NA may be more sensitive to novelty than other DA systems. Dopamine Novelty C57BL/6 DBA/2 Mice Inbred strains IT IS well documented that brain dopamine systems play impor- tant roles in various behavioral and neurochemical changes re- lated to stress (6,10,13). Research in this field has also shown that the several brain dopamine systems may not be as uniform in response to stressors as previously thought; however, not all researchers are in agreement. One of the areas of dispute con- cerns the effect of mild stressors (e.g., exposure to a novel environment), on brain dopamine systems. Some researchers have suggested that exposure to a novel environment may acti- vate dopamine metabolism in the frontal cortex selectively in certain strains of mice (131, while others have indicated that exposure to a novel environment alone had no effect on dopamine metabolism in the frontal cortex (2,3,5). The purpose of our experiment was to investigate the effect of exposure to a novel environment on brain dopamine and serotonin systems in geneti- cally defined C57BL/6 and DBA/2 mice, to determine whether genetic constitution might be involved in the apparently disparate results. The goals of this research were twofold. First, by examin- ing the effect of exposure to a novel environment brain dopamine and serotonin function, we can determine whether exposure to a novel environment is an effective stressor in terms of central dopamine response in male and female B6 and D2 mice, and if so, whether it selectively activates dopamine subsystems. Second, by comparing dopamine system- and subsystem activity in genet- ically different strains of mice, we can attempt to find a genetic basis for individual differences in response to novelty. Recently, we reported large differences between these same two strains in behavioral habituation to a novel environment (81, with B6 mice showing greater decreases in locomotor activity over the first 30 min after receiving an IP injection and being placed into a novel environment than did their D2 counterparts. METHOD Animals Eighty male and female C57BL/6 (B6) and DBA/2 (D2) mice (n = 10 per strain, sex, and treatment combination), age 60-80 days, were used in the experiments. All animals were derived from our stocks and caged in unisex sibling groups of two to three with water and food available ad lib in our vivarium. ’ Requests for reprints should be addressed to Dr. Byron C. Jones, Program in Biobehavioral Health, 210 Health and Human Development Building East, The Pennsylvania State University, University Park, PA 16802-6508. 361