Phasic Dopamine Release Evoked by Abused Substances Requires Cannabinoid Receptor Activation

Cannabinoid-1 receptors (CB 1 ) have an important role in nicotine reward and their function is disrupted by chronic nicotine exposure, suggesting nicotine-induced alterations in endocannabinoid (eCB) signaling. However, the effects of nicotine on brain eCB levels have not been rigorously evaluated. Volitional intake of nicotine produces physiological and behavioral effects distinct from forced drug administration, although the mechanisms underlying these effects are not known. This study compared the effects of volitional nicotine self-administration (SA) and forced nicotine exposure (yoked administration (YA)) on levels of eCBs and related neuroactive lipids in the ventral tegmental area (VTA) and other brain regions. Brain lipid levels were indexed both by in vivo microdialysis in the VTA and lipid extractions from brain tissues. Nicotine SA, but not YA, reduced baseline VTA dialysate oleoylethanolamide (OEA) levels relative to nicotine-naïve controls, and increased anandamide (AEA) release during nicotine intake. In contrast, all nicotine exposure paradigms increased VTA dialysate 2-arachidonoyl glycerol (2-AG) levels. Thus, nicotine differentially modulates brain lipid (2-AG, AEA, and OEA) signaling, and these modulations are influenced by the volitional nature of the drug exposure. Corresponding bulk tissue analysis failed to identify these lipid changes. Nicotine exposure had no effect on fatty acid amide hydrolase activity in the VTA, suggesting that changes in AEA and OEA signaling result from alterations in their nicotine-induced biosynthesis. Both CB 1 (by AEA and 2-AG) and non-CB 1 (by OEA) targets can alter the excitability and activity of the dopaminergic neurons in the VTA. Collectively, these findings implicate disrupted lipid signaling in the motivational effects of nicotine.

Section: Introductionmentioning

confidence: 92%

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

Buczynski

Polis

Parsons

2012

“…Drugs of abuse increase dopaminergic transmission in the NAc (Cheer et al, 2007;Daberkow et al, 2013;Di Chiara and Imperato, 1988;Phillips et al, 2003;Volkow et al, 2007), which contributes to their acutely reinforcing properties. We used a dose of morphine that, when paired with precipitated withdrawal, generates rapid dependence in rats (Schulteis et al, 1999).…”

Section: Morphine-exposure Increases Dopaminergic Transmission In Thementioning

confidence: 99%

Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal

Fox

Rodeberg

Wightman

2016

Dysregulated catecholamine signaling has long been implicated in drug abuse. Although much is known about adaptations following chronic drug administration, little work has investigated how a single drug exposure paired with withdrawal influences catecholamine signaling in vivo. We used fast-scan cyclic voltammetry in freely moving rats to measure real-time catecholamine overflow during acute morphine exposure and naloxone-precipitated withdrawal in two regions associated with the addiction cycle: the dopamine-dense nucleus accumbens (NAc) and norepinephrine-rich ventral bed nucleus of the stria terminalis (vBNST). We compared dopamine transients in the NAc with norepinephrine concentration changes in the vBNST, and correlated release with specific withdrawal-related behaviors. Morphine increased dopamine transients in the NAc, but did not elicit norepinephrine responses in the vBNST. Conversely, dopamine output was decreased during withdrawal, while norepinephrine was released in the vBNST during specific withdrawal symptoms. Both norepinephrine and withdrawal symptoms could be elicited in the absence of morphine by administering naloxone with an α 2 antagonist. The data support reciprocal roles for dopamine and norepinephrine signaling during drug exposure and withdrawal. The data also support the allostasis model and show that negative-reinforcement may begin working after a single exposure/withdrawal episode.

“…The mesolimbic dopamine system is implicated in reinforcement learning, goal-directed behavior, and motivational processes, including those for abused substances (Everitt and Robbins, 2005;Kelley, 2004;Robinson and Berridge, 1993;Salmone and Correa, 2012;Schultz, 2007). Alcohol, similar to virtually all abused substances, increases dopamine transmission within the ventral striatum (Cheer et al, 2007;Di Chiara and Imperato 1986;. Importantly, the mesolimbic dopamine system continues to mature during the adolescent period (Chambers et al, 2003), suggesting that adolescent alcohol use may alter its function, resulting in abnormal reward-related learning processes that impact decision making (Alaux-Cantin et al, 2013;Casey and Jones 2010;Goudriaan et al, 2007;Johnson et al, 2008;McClory and Spear 2014;Nasrallah et al, 2011;Philpot et al, 2009;Toalston et al, 2014;Zeigler et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive Cues Through Potentiation of Phasic Dopamine Signaling

Spoelder

Tsutsui

Lesscher

et al. 2015

Adolescent alcohol use remains a major public health concern due in part to well-established findings implicating the age of onset in alcohol use in the development of alcohol use disorders and persistent decision-making deficits in adults. We have previously demonstrated that moderate adolescent alcohol consumption in rats promotes suboptimal decision making and an associated perturbation in mesolimbic dopamine transmission in adulthood. Dopamine-dependent incentive learning processes are an integral component of value-based decision making and a fundamental element to many theoretical accounts of addiction. Thus we tested the hypothesis that adolescent alcohol use selectively alters incentive learning processes through perturbation of mesolimbic dopamine systems. To assess incentive learning, behavioral and neurochemical measurements were made during the acquisition, maintenance, extinction, and reacquisition of a Pavlovian conditioned approach procedure in adult rats with a history of adolescent alcohol consumption. We show that moderate adolescent alcohol consumption potentiates stimulus-evoked phasic dopamine transmission, measured in vivo by fast-scan cyclic voltammetry, in adulthood and biases individuals toward a dopamine-dependent incentive learning strategy. Moreover, we demonstrate that animals exposed to alcohol in adolescence are more sensitive to an unexpected variation in reward outcomes. This pattern of phasic dopamine signaling and the associated bias in learning may provide a mechanism for the well-documented vulnerability of individuals with early-life alcohol use for alcohol use disorders in adulthood.