Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum

Abstract

Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500nM) induced a decrease in dopamine efflux at low frequency (single pulse or 5 pulses at 10Hz) and an increase at high frequency (100Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake

“…[67][68][69][70] Nicotine also potentiates behavioral responding for numerous drugs of abuse, such as cocaine, 71,72 and increases release of dopamine in the nucleus accumbens. [73][74][75] High fat and sugar foods drive both dopamine release in the nucleus accumbens and compulsive consumption very similar to that seen with drugs of abuse. 71,76 Indeed, just as nicotine potentiates hedonic responding for cocaine, it also potentiates responding on a progressive ratio task for sucrose pellets.…”

A neural network for intermale aggression to establish social hierarchy

“…Since the identification of the action potential in 1939, it has become apparent that information processing does not follow a linear function between neurons connected through chemical synapses [101][102][103][104] . From the discovery of frequency tuning of terminals to respond to impulses arriving at a specific frequency 103,105 , to the identification of the packaging of small neurotransmitters and neuropeptides in small clear and large dense-core vesicles respectively [106][107][108][109][110][111] , the list of rules which governs neural communication is longer than originally thought or often considered in the field of systems neuroscience.…”

“…The initial investigations looking into the link between AP firing frequency and dopamine output, focused on the nigrostriatal system due to its prominent role in health and disease 103,[112][113][114][115] . In this system, work by Francois Gonon identified the relationship between impulse flow and DA release in the striatum 116 .…”

Complex Control of Striatal Neurotransmission by Nicotinic Acetylcholine Receptors via Excitatory Inputs onto Medium Spiny Neurons

“…To further decrease smoking prevalence, it is thus imperative to identify factors that may contribute to the development of nicotine addiction. Even though the reinforcing properties of nicotine primarily have been attributed to the mesolimbic dopamine system (Singer et al, 1982;Grenhoff et al, 1986;Benwell and Balfour, 1992;Corrigall, 1999;Di Chiara, 2000), later research has put forward dorsal striatum as a key mediator of several rewardrelated behaviors, including locomotor sensitization (Bamford et al, 2008), cue-dependent drug-seeking (Quintana et al, 2012), and compulsive drug-seeking habits (Yin et al, 2004;Vanderschuren et al, 2005;Everitt and Robbins, 2016). Dorsal striatum has especially been implicated in later stages of addiction, where there appears to be a neuroanatomical progression from ventral striatal to dorsal striatal control over drug-seeking behavior (Gerdeman et al, 2003;Volkow et al, 2006;Yin et al, 2008).…”

“…Especially, nAChR activation has been reported to trigger GABAergic interneurons (English et al, 2011;Luo et al, 2013), which could indirectly alter dopaminergic firing and striatal output (Koó s et al, 2004;Adermark et al, 2011a;Clarke and Adermark, 2015;Silberberg and Bolam, 2015). In addition, the effect displayed by nicotine appears to depend on baseline firing frequency (Koó s and Tepper, 2002;Goutier et al, 2016). Indeed, reduced activation of nAChRs has been postulated to enhance dopamine bursts at high frequencies while depressing dopamine release at lower frequencies, suggesting that nAChRs may work as a presynaptic filter to differentially govern dopamine release depending on neuronal activity (Rice and Cragg, 2004).…”