Dopamine Signaling Differences in the Nucleus Accumbens and Dorsal Striatum Exploited by Nicotine

Abstract

The dorsal striatum and the nucleus accumbens (NAc) shell of the ventral striatum have similar cellular components and are both richly innervated by dopamine neurons. Despite similarities that extend throughout the striatum, only the NAc shell has a conspicuous increase in basal dopamine upon the initial administration of psychostimulant drugs such as nicotine. As measured by microdialysis, the elevated dopamine in the NAc shell is considered an identifying functional characteristic of addictive drugs. To examine this general functional difference between nicotine's action on the dorsolateral striatum and NAc shell, we directly monitored dopamine release in rat striatal slices using fast-scan cyclic voltammetry. In addition, we separately monitored the in vivo unit firing activity of putative midbrain dopamine neurons from freely moving rats using chronic multiple tetrodes. Nicotine administration increased the firing frequency of dopamine neurons and specifically increased the number and the length of phasic burst firing. The frequency dependence for dopamine release in the dorsolateral striatum and NAc shell is fundamentally different, enabling mainly the NAc shell to capitalize on the nicotineinduced phasic burst firing by dopamine neurons. Although nicotine decreased low-frequency (tonic) dopamine release in both areas, the increased ratio of phasic bursts relative to tonic firing caused by nicotine boosted the basal dopamine concentration predominantly in the NAc shell. By favoring release from bursts while depressing release from tonic signals, nicotine spreads the range of dopamine signaling and effectively increases the signal-to-noise relationship along dopamine afferents.

Nicotinic acetylcholine receptors and the ascending dopamine pathways

“…The striatum can be subdivided anatomically and functionally (see Appendix) and there is evidence for α6β2* having a greater role in the NAc than in the dorsal striatum [57,83]. A similar conclusion was reached by Drenan et al striatum with respect to dopamine release probability was shown using FSCV [16]. The extent to which α6β2* nAChRs contribute to this difference is not known.…”

“…Extrapolation between in vivo and in vitro studies is also problematic as inherent firing patterns may not be preserved in the latter. A recent study [16] overcame this problem by recording firing patterns from midbrain dopamine neurons of freely moving rats in vivo and subsequently reproducing the same firing rates in striatal slices in vitro, allowing for a measurement of dopamine release probability across the striatum during firing modes representative of nicotine administration in the midbrain. …”

Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal

“…Although the amount of DA released via tonic neuronal activity is small in comparison with that via phasic activity, a previous study showed that tonic DA activity is independent of burst-firing and provides sufficient DA to engage behavior (14), thus it is plausible that a tonic DA signal mediates the behavioral response to nicotine withdrawal. A single injection of nicotine leads to the large-scale phasic release of DA (16,17); therefore, it is possible that nicotine-dependent subjects who are experiencing withdrawal may take nicotine to temporarily modulate DA levels in the brain by increasing release through phasic activation of VTA DA neurons. This hypothesis is similar to Grace's tonic/phasic model of DA system regulation (7).…”

“…The phasic and tonic activities of DA neurons are thought to mediate different aspects of goal-directed behavior; phasic activity facilitates cue-reward association and acquisition of incentive salience, whereas tonic activity is involved in response inhibition and behavioral flexibility (5,6,14). Consistent with its motivational properties, a single systemic nicotine injection increases phasic activity in the ventral tegmental area (VTA) (15) and the release of DA in the ventral striatum (16,17), and chronic exposure to nicotine decreases tonic, but not phasic, DA activity in the VTA (18). However, the role of tonic activity and the D1R vs. phasic activity and the D2R in signaling the motivational effects of acute nicotine and withdrawal from chronic nicotine is unknown.…”

Dopaminergic Signaling Mediates the Motivational Response Underlying the Opponent Process to Chronic but Not Acute Nicotine

“…These results suggest that nicotine motivation in nicotine dependent and withdrawn animals is driven by a DA-dependent aversion to nicotine withdrawal. Dopaminergic signaling after nicotine administration is a complex phenomenon involving tonic and phasic DA activity (Rice and Cragg, 2004;Zhang and Sulzer, 2004;Zhang et al, 2009). Withdrawal from nicotine changes the activity of DA neurons in the VTA and the release of DA in the nucleus accumbens (Hildebrand et al, 1998;Rada et al, 2001;Liu and Jin, 2004), leading to a change in the specific pattern of DA signaling at the postsynaptic level.…”