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Role of accumbens nicotinic acetylcholine receptors in cue-induced nicotine seeking and synaptic plasticity
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Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Role of accumbens nicotinic acetylcholine receptors in cue-induced nicotine seeking and synaptic plasticity Armani del Franco 1,2,∗ , Gregory Powell 1,2 , Broc Pagni 1 , Julianna Goenaga 1 , Michael Scofield 3 , Cassandra Gipson-Reichardt 1 1 Psychology, Arizona State University, Tempe, AZ, United States 2 School of Life Sciences, Arizona State University, Tempe, AZ, United States 3 Neurosciences, Medical University of South Carolina, Charleston, SC, United States
Aims: Addiction to nicotine (NIC) produces long-term changes in brain synaptic physiology that could contribute to relapse vulnerability. Understanding the neurobiology is important in identifying novel pharmacotherapies. In the nucleus accumbens core (NAcore), glutamatergic signaling and synaptic plasticity has been shown to be involved in cue-induced nicotine seeking and are modulated by nicotinic acetylcholine receptors (nAChRs). We therefore investigated the effects of two intra-NAcore nAChR antagonists, methylyllcaconitine (MLA) or dihydro--erythroidine (DHE), on cue-induced NIC seeking and relapse-associated synaptic plasticity as measured by changes in dendritic spines on NAcore medium spiny neurons. Methods: Male Sprague Dawley rats were trained to selfadminister NIC (0.02 mg/kg/infusion, paired with a light + tone cue). Rats were then placed into extinction for 14 days. Following intraNAcore infusion of either MLA (11 nmol), DHE (84 nmol), or aCSF, rats were placed into cue-induced reinstatement for 15 min. Rats were then transcardially perfused, and tissue was prepared for morphological analysis. Results: Both MLA and DHE inhibited cue-induced NIC seeking compared to vehicle treated animals, as evidenced by a significant reduction in active lever presses for nicotine-paired cues. MLA, but not DHE, inhibited the rapid, transient increase in spine head diameter compared to vehicle at 15 min. Conclusions: Our results show that both NAcore nAchRs mediate cue-induced NIC seeking. However, morphological analysis indicates that only MLA inhibits relapse associated synaptic plasticity, suggesting a potential role of ␣7 nAchRs but not ␣42. The location of these receptors as well as their ability to modulate glutamate transmission and synaptic activity within the NAcore remains unclear, thus future research will explore the impact of acetylcholine signaling on neurotransmission and synaptic plasticity. Financial support: NIDA R00DA036569.
Are DSM-5 criteria for sud transferable to food addiction? IRT analysis for alcohol, tobacco, cannabis, opiate and food addiction in a clinical sample Cecile Marianne Denis 1,2,∗ , Marco Aurélio Camargo da Rosa 2,4 , Fuschia Serre 2 , C. Kervran 2 , Maud Henry 3 , B. Cherifi 3 , Marc Auriacombe 1,2 , M. Fatseas 2 1
University Pennsylvania, Philadelphia, PA, United States 2 Addiction Psychiatry, University Bordeaux/CNRS USR 3413, Bordeaux, France 3 Obesity Clinic, CHU de Bordeaux, Bordeaux, France 4 University Rio Grande, Porto Allegre, Brazil Aims: Some studies showed that DSM-5 criteria for SUD might be transferable to Food Addiciton (FA). We aimed to examine criterion severity and discrimination for FA and to compare them with SUD criteria for alcohol, tobacco, cannabis and opiates. Methods: Patients from addiction and obesity clinics in Bordeaux (France, EU) were assessed with the modified ASI, the Mini International Neuropsychiatric Interview, DSM-5 criteria for SUD and FA criteria based on DSM-5 criteria for SUD. We ran 2parameter logistic item response theory (IRT) model and ranked criteria by their estimated severity. To quantify the similarity in severity ranking of the criteria across substance and food, we computed Spearman correlations. Results: 730 consecutive patients were enrolled. 66% males, mean age 41.5 years (SD = 67). Current use of tobacco (n = 423), alcohol (n = 422), cannabis (n = 372), opiates (n = 149) or food-related disorders (n = 143). The prevalence of each endorsed criteria varied across substance and food disorders, however the same 3 criteria (using in larger amount, unsuccessful attempt to cut down, and craving) were found among the most prevalent across groups. Discrimination parameters across groups ranged from 0.55 to 9.40, with FA criteria exhibiting the highest discrimination estimates. Severity rankings of the criteria were not identical across substances and food addiction. However, correlations were high between food and tobacco (r = 0.92) and food and opiates (r = 0.59). Conclusions: FA criteria, as SUD criteria, have a strong ability to delineate subjects. The correlations between food and other substances (tobacco, opiates) indicate that the criteria have similar patterns of severity. These findings showed that SUD criteria could be applicable to diagnose FA. Financial support: PHRC 2006, CSF, CNPq, CAPES. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.155
http://dx.doi.org/10.1016/j.drugalcdep.2016.08.154 Associations between educational attainment, smoking history, quit attempts and interest in quitting Rachel Denlinger 2,∗ , Jennifer W. Tidey 2 , Dorothy Hatsukami 3 , Eric Donny 1 1 University of Pittsburgh, Pittsburgh, PA, United States 2 Brown University, Providence, RI, United States 3 University of Minnesota, Minneapolis, MN, United States
Aims: A recent multisite clinical trial of non-treatment seeking smokers assessed the impact of smoking cigarettes that varied in nicotine content on smoking behavior during a 6-week intervention. For this secondary analysis, we examined whether educational attainment was associated with differences in tobacco use history,
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Role of accumbens nicotinic acetylcholine receptors in cue-induced nicotine seeking and synaptic plasticity Armani del Franco 1,2,∗ , Gregory Powell 1,2 , Broc Pagni 1 , Julianna Goenaga 1 , Michael Scofield 3 , Cassandra Gipson-Reichardt 1 1 Psychology, Arizona State University, Tempe, AZ, United States 2 School of Life Sciences, Arizona State University, Tempe, AZ, United States 3 Neurosciences, Medical University of South Carolina, Charleston, SC, United States
Aims: Addiction to nicotine (NIC) produces long-term changes in brain synaptic physiology that could contribute to relapse vulnerability. Understanding the neurobiology is important in identifying novel pharmacotherapies. In the nucleus accumbens core (NAcore), glutamatergic signaling and synaptic plasticity has been shown to be involved in cue-induced nicotine seeking and are modulated by nicotinic acetylcholine receptors (nAChRs). We therefore investigated the effects of two intra-NAcore nAChR antagonists, methylyllcaconitine (MLA) or dihydro--erythroidine (DHE), on cue-induced NIC seeking and relapse-associated synaptic plasticity as measured by changes in dendritic spines on NAcore medium spiny neurons. Methods: Male Sprague Dawley rats were trained to selfadminister NIC (0.02 mg/kg/infusion, paired with a light + tone cue). Rats were then placed into extinction for 14 days. Following intraNAcore infusion of either MLA (11 nmol), DHE (84 nmol), or aCSF, rats were placed into cue-induced reinstatement for 15 min. Rats were then transcardially perfused, and tissue was prepared for morphological analysis. Results: Both MLA and DHE inhibited cue-induced NIC seeking compared to vehicle treated animals, as evidenced by a significant reduction in active lever presses for nicotine-paired cues. MLA, but not DHE, inhibited the rapid, transient increase in spine head diameter compared to vehicle at 15 min. Conclusions: Our results show that both NAcore nAchRs mediate cue-induced NIC seeking. However, morphological analysis indicates that only MLA inhibits relapse associated synaptic plasticity, suggesting a potential role of ␣7 nAchRs but not ␣42. The location of these receptors as well as their ability to modulate glutamate transmission and synaptic activity within the NAcore remains unclear, thus future research will explore the impact of acetylcholine signaling on neurotransmission and synaptic plasticity. Financial support: NIDA R00DA036569.
Are DSM-5 criteria for sud transferable to food addiction? IRT analysis for alcohol, tobacco, cannabis, opiate and food addiction in a clinical sample Cecile Marianne Denis 1,2,∗ , Marco Aurélio Camargo da Rosa 2,4 , Fuschia Serre 2 , C. Kervran 2 , Maud Henry 3 , B. Cherifi 3 , Marc Auriacombe 1,2 , M. Fatseas 2 1
University Pennsylvania, Philadelphia, PA, United States 2 Addiction Psychiatry, University Bordeaux/CNRS USR 3413, Bordeaux, France 3 Obesity Clinic, CHU de Bordeaux, Bordeaux, France 4 University Rio Grande, Porto Allegre, Brazil Aims: Some studies showed that DSM-5 criteria for SUD might be transferable to Food Addiciton (FA). We aimed to examine criterion severity and discrimination for FA and to compare them with SUD criteria for alcohol, tobacco, cannabis and opiates. Methods: Patients from addiction and obesity clinics in Bordeaux (France, EU) were assessed with the modified ASI, the Mini International Neuropsychiatric Interview, DSM-5 criteria for SUD and FA criteria based on DSM-5 criteria for SUD. We ran 2parameter logistic item response theory (IRT) model and ranked criteria by their estimated severity. To quantify the similarity in severity ranking of the criteria across substance and food, we computed Spearman correlations. Results: 730 consecutive patients were enrolled. 66% males, mean age 41.5 years (SD = 67). Current use of tobacco (n = 423), alcohol (n = 422), cannabis (n = 372), opiates (n = 149) or food-related disorders (n = 143). The prevalence of each endorsed criteria varied across substance and food disorders, however the same 3 criteria (using in larger amount, unsuccessful attempt to cut down, and craving) were found among the most prevalent across groups. Discrimination parameters across groups ranged from 0.55 to 9.40, with FA criteria exhibiting the highest discrimination estimates. Severity rankings of the criteria were not identical across substances and food addiction. However, correlations were high between food and tobacco (r = 0.92) and food and opiates (r = 0.59). Conclusions: FA criteria, as SUD criteria, have a strong ability to delineate subjects. The correlations between food and other substances (tobacco, opiates) indicate that the criteria have similar patterns of severity. These findings showed that SUD criteria could be applicable to diagnose FA. Financial support: PHRC 2006, CSF, CNPq, CAPES. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.155
http://dx.doi.org/10.1016/j.drugalcdep.2016.08.154 Associations between educational attainment, smoking history, quit attempts and interest in quitting Rachel Denlinger 2,∗ , Jennifer W. Tidey 2 , Dorothy Hatsukami 3 , Eric Donny 1 1 University of Pittsburgh, Pittsburgh, PA, United States 2 Brown University, Providence, RI, United States 3 University of Minnesota, Minneapolis, MN, United States
Aims: A recent multisite clinical trial of non-treatment seeking smokers assessed the impact of smoking cigarettes that varied in nicotine content on smoking behavior during a 6-week intervention. For this secondary analysis, we examined whether educational attainment was associated with differences in tobacco use history,