scholarly journals A neural substrate of compulsive alcohol use

2021 ◽  
Vol 7 (34) ◽  
pp. eabg9045
Author(s):  
Esi Domi ◽  
Li Xu ◽  
Sanne Toivainen ◽  
Anton Nordeman ◽  
Francesco Gobbo ◽  
...  
Keyword(s):  
Large Population ◽  
Brain Network ◽  
Alcohol Addiction ◽  
Central Nucleus ◽  
Inhibitory Neurons ◽  
Self Administration ◽  
Core Element ◽  
Neural Substrate ◽  
Activity Dependent ◽  
Administration Procedure

Alcohol intake remains controlled in a majority of users but becomes “compulsive,” i.e., continues despite adverse consequences, in a minority who develop alcohol addiction. Here, using a footshock-punished alcohol self-administration procedure, we screened a large population of outbred rats to identify those showing compulsivity operationalized as punishment-resistant self-administration. Using unsupervised clustering, we found that this behavior emerged as a stable trait in a subpopulation of rats and was associated with activity of a brain network that included central nucleus of the amygdala (CeA). Activity of PKCδ+ inhibitory neurons in the lateral subdivision of CeA (CeL) accounted for ~75% of variance in punishment-resistant alcohol taking. Activity-dependent tagging, followed by chemogenetic inhibition of neurons activated during punishment-resistant self-administration, suppressed alcohol taking, as did a virally mediated shRNA knockdown of PKCδ in CeA. These findings identify a previously unknown mechanism for a core element of alcohol addiction and point to a novel candidate therapeutic target.

A drug-vs-food “choice” self-administration procedure in rats to investigate pharmacological and environmental mechanisms of substance use disorders

2021 ◽  
Vol 354 ◽  
pp. 109110
Author(s):  
E. Andrew Townsend ◽  
Kathryn L. Schwienteck ◽  
Hannah L. Robinson ◽  
Stephen T. Lawson ◽  
Matthew L. Banks
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Food Choice ◽  
Self Administration ◽  
Administration Procedure

scholarly journals Effects of adolescent caffeine consumption on cocaine self-administration and reinstatement of cocaine seeking

2018 ◽  
Vol 33 (1) ◽  
pp. 132-144
Author(s):  
Tracey A Larson ◽  
Casey E O’Neill ◽  
Michaela P Palumbo ◽  
Ryan K Bachtell
Keyword(s):  
Dose Response ◽  
Extinction Training ◽  
Schedules Of Reinforcement ◽  
Sprague Dawley ◽  
Self Administration ◽  
Caffeine Consumption ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Cocaine Seeking ◽  
Administration Procedure

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.

scholarly journals A brain network that supports consensus-seeking and conflict-resolving of college couples’ shopping interaction

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
HanShin Jo ◽  
Chiu-Yueh Chen ◽  
Der-Yow Chen ◽  
Ming-Hung Weng ◽  
Chun-Chia Kung
Keyword(s):  
Brain Network ◽  
The Other ◽  
Inferior Parietal Lobule ◽  
Social Decision ◽  
Decision Network ◽  
Fmri Study ◽  
The Social ◽  
Neural Substrate ◽  
Preference Ratings ◽  
Parietal Lobule

Abstract One of the typical campus scenes is the social interaction between college couples, and the lesson couples must keep learning is to adapt to each other. This fMRI study investigated the shopping interactions of 30 college couples, one lying inside and the other outside the scanner, beholding the same item from two connected PCs, making preference ratings and subsequent buy/not-buy decisions. The behavioral results showed the clear modulation of significant others’ preferences onto one’s own decisions, and the contrast of the “shop-together vs. shop-alone”, and the “congruent (both liked or disliked the item, 68%) vs. incongruent (one liked but the other disliked, and vice versa)” together trials, both revealed bilateral temporal parietal junction (TPJ) among other reward-related regions, likely reflecting mentalizing during preference harmony. Moreover, when contrasting “own-high/other-low vs. own-low/other-high” incongruent trials, left anterior inferior parietal lobule (l-aIPL) was parametrically mapped, and the “yield (e.g., own-high/not-buy) vs. insist (e.g., own-low/not-buy)” modulation further revealed left lateral-IPL (l-lIPL), together with left TPJ forming a local social decision network that was further constrained by the mediation analysis among left TPJ–lIPL–aIPL. In sum, these results exemplify, via the two-person fMRI, the neural substrate of shopping interactions between couples.

scholarly journals Nociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA–GABA transmission in highly addicted rats

2020 ◽  
Vol 117 (4) ◽  
pp. 2140-2148 ◽  
Author(s):  
Marsida Kallupi ◽  
Lieselot L. G. Carrette ◽  
Jenni Kononoff ◽  
Leah C. Solberg Woods ◽  
Abraham A. Palmer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Opioid Use Disorder ◽  
Central Nucleus ◽  
Orphanin Fq ◽  
Opioid Use ◽  
Self Administration ◽  
Endogenous Opioid ◽  
Electrophysiological Recordings ◽  
Gaba Transmission

Approximately 25% of patients who are prescribed opioids for chronic pain misuse them, and 5 to 10% develop an opioid use disorder. Although the neurobiological target of opioids is well known, the molecular mechanisms that are responsible for the development of addiction-like behaviors in some but not all individuals are poorly known. To address this issue, we used a unique outbred rat population (heterogeneous stock) that better models the behavioral and genetic diversity that is found in humans. We characterized individual differences in addiction-like behaviors using an addiction index that incorporates the key criteria of opioid use disorder: escalated intake, highly motivated responding, and hyperalgesia. Using in vitro electrophysiological recordings in the central nucleus of the amygdala (CeA), we found that rats with high addiction-like behaviors (HA) exhibited a significant increase in γ-aminobutyric acid (GABA) transmission compared with rats with low addiction-like behaviors (LA) and naive rats. The superfusion of CeA slices with nociceptin/orphanin FQ peptide (N/OFQ; 500 nM), an endogenous opioid-like peptide, normalized GABA transmission in HA rats. Intra-CeA levels of N/OFQ were lower in HA rats than in LA rats. Intra-CeA infusions of N/OFQ (1 μg per site) reversed the escalation of oxycodone self-administration in HA rats but not in LA rats. These results demonstrate that the downregulation of N/OFQ levels in the CeA may be responsible for hyper-GABAergic tone in the CeA that is observed in individuals who develop addiction-like behaviors. Based on these results, we hypothesize that small molecules that target the N/OFQ system might be useful for the treatment of opioid use disorder.

scholarly journals Noradrenergic neurons in the rat solitary nucleus participate in the esophageal-gastric relaxation reflex

2003 ◽  
Vol 285 (2) ◽  
pp. R479-R489 ◽  
Author(s):  
R. C. Rogers ◽  
R. A. Travagli ◽  
G. E. Hermann
Keyword(s):  
Large Population ◽  
Central Nucleus ◽  
Motor Nucleus ◽  
Adrenoceptor Antagonist ◽  
Dorsal Motor Nucleus ◽  
Efferent Neurons ◽  
Nos Inhibitor ◽  
Immunohistochemical Techniques ◽  
Oxide Synthase ◽  
Local Brain

Activation of esophageal mechanosensors excites neurons in and near the central nucleus of the solitary tract (NSTc). In turn, NSTc neurons coordinate the relaxation of the stomach [i.e., the receptive relaxation reflex (RRR)] by modulating the output of vagal efferent neurons of the dorsal motor nucleus of the vagus (DMN). The NSTc area contains neurons with diverse neurochemical phenotypes, including a large population of catecholaminergic and nitrergic neurons. The aim of the present study was to determine whether either one of these prominent neuronal phenotypes was involved in the RRR. Immunohistochemical techniques revealed that repetitive esophageal distension caused 53% of tyrosine hydroxylase-immunoreactive (TH-ir) neurons to colocalize c-Fos in the NSTc. No nitric oxide synthase (NOS)-ir neurons in the NSTc colocalized c-Fos in either distension or control conditions. Local brain stem application (2 ng) of α-adrenoreceptor antagonists (i.e., α1-prazosin or α2-yohimbine) significantly reduced the magnitude of the esophageal distension-induced gastric relaxation to ∼55% of control conditions. The combination of yohimbine and prazosin reduced the magnitude of the reflex to ∼27% of control. In contrast, pretreatment with either the NOS-inhibitor NG-nitro-l-arginine methyl ester or the β-adrenoceptor antagonist propranolol did not interfere with esophageal distension-induced gastric relaxation. Unilateral microinjections of the agonist norepinephrine (0.3 ng) directed at the DMN were sufficient to mimic the transient esophageal-gastric reflex. Our data suggest that noradrenergic, but not nitrergic, neurons of the NSTc play a prominent role in the modulation of the RRR through action on α1- and α2-adrenoreceptors. The finding that esophageal afferent stimulation alone is not sufficient to activate NOS-positive neurons in the NSTc suggests that these neurons may be strongly gated by other central nervous system inputs, perhaps related to the coordination of swallowing or emesis with respiration.

scholarly journals The network properties of the brain at the time of normal birth support the acquisition of language processing

2018 ◽  
Author(s):  
Piergiorgio Salvan ◽  
Tomoki Arichi ◽  
Diego Vidaurre ◽  
J Donald Tournier ◽  
Shona Falconer ◽  
...  
Keyword(s):  
Language Acquisition ◽  
Language Processing ◽  
Developmental Trajectories ◽  
Brain Structures ◽  
Brain Network ◽  
Language Abilities ◽  
Normal Birth ◽  
Neural Substrate ◽  
Network Properties ◽  
The Brain

AbstractLanguage acquisition appears to rely at least in part on recruiting pre-existing brain structures. We hypothesized that the neural substrate for language can be characterized by distinct, non-trivial network properties of the brain, that modulate language acquisition early in development. We tested whether these brain network properties present at the normal age of birth predicted later language abilities, and whether these were robust against perturbation by studying infants exposed to the extreme environmental stress of preterm birth.We found that brain network controllability and integration predicted respectively phonological, ‘bottom-up’ and syntactical, ‘top-down’ language skills at 20 months, and that syntactical but not phonological functions were modulated by premature extrauterine life. These data show that the neural substrate for language acquisition is a network property present at term corrected age. These distinct developmental trajectories may be relevant to the emergence of social interaction after birth.

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