Research reportRegional and temporal differences in real-time dopamine efflux in the nucleus accumbens during free-choice novelty
Introduction
Rats, monkeys, and other mammalian species show a preference for novel stimuli and will actively explore a novel environment 8, 16, 33. Although multiple brain mechanisms are undoubtedly involved in such behavioral responses, ample evidence suggests a critical role for dopamine (DA) transmission in the limbic forebrain, especially the nucleus accumbens [6]. In fact, novelty-seeking behavior is reduced by either neurotoxic destruction of accumbal DA terminals [41]or accumbal application of DA receptor antagonists 12, 21. These and related findings prompt the question of how DA released in the nucleus accumbens participates in the behavioral response to novelty.
Attempts to address the question of novelty-related accumbal DA release are confronted with several important issues. First, DA involvement in the novelty response is likely to be brief. The ventral tegmental area, which is the major source of DA input to the nucleus accumbens, is activated by novel stimuli for only a few seconds [49]. This finding is supported by evidence of a novelty-related change in accumbal catechols recorded at 1-min intervals [40]but not when sampling times increase to 10 min [13]. Prolonged recording procedures, therefore, may be relatively insensitive to novelty-related changes in DA transmission. Second, the nucleus accumbens is a heterogeneous structure, consisting of at least two anatomically and behaviorally distinct regions: a limbic-related shell and a striatal-related core 32, 57. These regions, moreover, are separated by a shell–core transition zone, the so-called shore, which may represent still another unique accumbal area [45]. Measurements of accumbal DA function, therefore, appear to require a high degree of spatial resolution. A final consideration is that apart from being rewarding, some aspects of novelty can be stressful, particularly in situations in which novelty is inescapable [39]. Accumbal DA is responsive to inescapable environmental stressors 1, 22as well as to rewarding stimuli that elicit approach responses 15, 31. Thus, accurate assessment of the rewarding component of novelty requires the use of a novelty test that is not stressful.
To deal with each of these issues, we combined fast-scan cyclic voltammetry at carbon-fiber electrodes with a free-choice novelty test. Fast-scan cyclic voltammetry can detect submicromolar levels of DA with a temporal resolution in the millisecond range 2, 51, 54. The small size of these electrodes, moreover, permits resolution of several different accumbal regions. Finally, to maximize the rewarding component of novelty, we used a test based on free choice rather than forced exposure. Whereas forced-exposure to novelty elevates blood corticosterone, the free-choice approach does not [34]. Our results indicate that entry into novelty enhances accumbal DA transmission, but regional differences in the time course of DA efflux suggest more than one role for DA in novelty-seeking behavior.
Section snippets
Animals
Data were obtained from 20 male, Sprague-Dawley rats bred in our colony from source animals supplied by Harlan Industries (Indianapolis, IN). All subjects were housed under standard laboratory conditions with unlimited access to food and water in the home cage. The experimental procedures were approved for use by the Indiana University Institutional Animal Care and Use Committee.
Fast-scan cyclic voltammetry
Our electrochemical recordings used the same surgical preparation procedures and data-collection instrumentation
In vitro testing of electrode selectivity
Voltammograms for DA as well as several potential interferent compounds were recorded at 300 V s−1. Consistent with previous results [7], the ascorbate and DOPAC voltammograms were readily distinguishable from those for DA and NE. These results are shown in Fig. 1. Note also that although DA and NE have similar voltammograms, the electrodes are at least 3-times more sensitive to DA.
Voltammetric recording during entry into novelty
Although some spontaneous behavior occurred in the familiar compartment during the final habituation session, all
Discussion
Ample neurochemical and pharmacological data indicate that a wide range of positively reinforcing stimuli enhance accumbal DA transmission 17, 26, 55. We now provide voltammetric evidence for a similar effect after entry into novelty. This effect is highly region specific, occurring in the shell and its narrow border zone with the core, but not in the core itself or in the overlying neostriatum. In view of the dense innervation the shell receives from limbic structures 9, 38, it seems likely
Acknowledgements
This research was supported by U.S. Public Health Service grants from the National Institute on Drug Abuse (DA 05312 and DA 02451). We also thank P.E. Langley for technical assistance, and F. Caylor for manuscript preparation. Drs. P.A. Garris and R.M. Wightman provided ongoing advice and commentary.
References (57)
In vivo electrochemical measurements in the CNS
Prog. Neurobiol.
(1990)- et al.
Intercellular communication in the brain: wiring versus volume transmission
Neuroscience
(1995) - et al.
Psychobiology of novelty seeking and drug seeking behavior
Behav. Brain Res.
(1996) - et al.
Nonlinear relationship between impulse flow, dopamine release and dopamine elimination in the rat brain in vivo
Neuroscience
(1994) - et al.
Pharmacological characterization of dopamine systems in the nucleus accumbens core and shell
Neuroscience
(1992) - et al.
Heterogeneity of evoked dopamine overflow within the striatal and striatoamygdaloid regions
Neuroscience
(1994) - et al.
The role of mesoaccumbens pallidal circuitry in novelty-induced behavioral activation
Neuroscience
(1995) - et al.
Repeated stressful experiences differently affect limbic dopamine release during and following stress
Brain Res.
(1992) - et al.
Multiple amphetamine injections reduce the release of ascorbic acid in the neostriatum of the rat
Brain Res.
(1986) - et al.
Principles of voltammetry and microelectrode surface states
J. Neurosci. Methods
(1993)