Presynaptic Opioid and Nicotinic Receptor Modulation of Dopamine Overflow in the Nucleus Accumbens

Abstract

Behaviorally relevant stimuli prompt midbrain dopamine (DA) neurons to switch from tonic to burst firing patterns. Similar shifts to burst activity are thought to contribute to the addictive effects of opiates and nicotine. The nucleus accumbens DA overflow produced by these drugs is a key element in their pathological effects. Using electrochemical techniques in brain slices, we explored the effects of opioids on single-spike and burst stimuli-evoked DA overflow in the dorsal and ventral striatum. In specific subregions of the nucleus accumbens, -opioids inhibit DA overflow elicited with single-spike stimuli while leaving that produced by burst stimuli unaffected. This is similar to published effects of nicotinic receptor blockade or desensitization, and is mediated by opioid receptor-induced inhibition of cholinergic interneurons. Whereas ␦-opioids have similar effects, -opioids inhibit evoked DA overflow throughout the striatum in a manner that is not overcome with high-frequency stimuli. These observations reveal remarkable mechanistic overlap between the effects of nicotine and opiates within the dopamine reward pathway.

Confronting a Neglected Epidemic: Tobacco Cessation for Persons with Mental Illnesses and Substance Abuse Problems

“…The effects of nicotine and opiates on the brain's reward system are equally potent in a key pleasure-sensing area of the brain: the nucleus accumbens (12).…”

Changes in mu-opioid receptor expression and function in the mesolimbic system after long-term access to a palatable diet

“…In the VTA, mu-opioid receptors are primarily expressed on GABA neuronal terminals (Johnson & North, 1992;Shoji et al, 1999;Bergevin et al, 2002;Matsui & Williams, 2011). In the NAc, mu-opioid receptors are expressed on cholinergic interneurons and on medium spiny neurons (Britt & McGehee, 2008;Ma et al, 2012).…”

μ- and δ-Opioid-Related Processes in the Accumbens Core and Shell Differentially Mediate the Influence of Reward-Guided and Stimulus-Guided Decisions on Choice

“…Although their exact localization may well differ according to region and subtype, MOR and DOR are thought to be predominantly expressed extrasynaptically on dendrites, dendritic shafts, and soma (Gracy et al, 1997;Svingos et al, 1997;Wang and Pickel, 1998), and to modulate the activity of medium spiny neurons both directly and indirectly through their influence on local acetylcholine and dopamine release (Svingos et al, , 1999Wang and Pickel, 1998). Some important differences could, however, explain their distinct functional influences; for example, there is evidence that DOR might also act presynaptically in the accumbens in a way that differs from MOR, particularly in the shell (Svingos et al, 1998;Britt and McGehee, 2008;Hipó lito et al, 2008). Nevertheless, there is much still to be discovered in this circuitry, and, as there are currently multiple alternative hypotheses as to the way in which CTAP and naltrindole could act differentially in core and shell to regulate distinct function, further research is currently ongoing to establish how this is achieved in the current situation.…”