scholarly journals Maternal Diet Influences the Reinstatement of Cocaine-Seeking Behavior and the Expression of Melanocortin-4 Receptors in Female Offspring of Rats

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1462
Author(s):  
Dawid Gawliński ◽  
Kinga Gawlińska ◽  
Małgorzata Frankowska ◽  
Małgorzata Filip
Keyword(s):  
Maternal Diet ◽  
Dorsal Striatum ◽  
Brain Structures ◽  
Female Offspring ◽  
Self Administration ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
Pregnancy And Lactation ◽  
The Impact ◽  
Cocaine Reward

Recent studies have emphasized the role of the maternal diet in the development of mental disorders in offspring. Substance use disorder is a major global health and economic burden. Therefore, the search for predisposing factors for the development of this disease can contribute to reducing the health and social damage associated with addiction. In this study, we focused on the impact of the maternal diet on changes in melanocortin-4 (MC-4) receptors as well as on behavioral changes related to cocaine addiction. Rat dams consumed a high-fat diet (HFD), high-sugar diet (HSD, rich in sucrose), or mixed diet (MD) during pregnancy and lactation. Using an intravenous cocaine self-administration model, the susceptibility of female offspring to cocaine reward and cocaine-seeking propensities was evaluated. In addition, the level of MC-4 receptors in the rat brain structures related to cocaine reward and relapse was assessed. Modified maternal diets did not affect cocaine self-administration in offspring. However, the maternal HSD enhanced cocaine-seeking behavior in female offspring. In addition, we observed that the maternal HSD and MD led to increased expression of MC-4 receptors in the nucleus accumbens, while increased MC-4 receptor levels in the dorsal striatum were observed after exposure to the maternal HSD and HFD. Taken together, it can be concluded that a maternal HSD is an important factor that triggers cocaine-seeking behavior in female offspring and the expression of MC-4 receptors.

scholarly journals Extinction vs. Abstinence: A Review of the Molecular and Circuit Consequences of Different Post-Cocaine Experiences

2021 ◽  
Vol 22 (11) ◽  
pp. 6113
Author(s):  
Marek Schwendt ◽  
Lori A. Knackstedt
Keyword(s):  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Dorsal Striatum ◽  
Extinction Training ◽  
Face Validity ◽  
Self Administration ◽  
Cocaine Seeking ◽  
Glutamate Receptor Antagonists ◽  
The Impact ◽  
Abstinence Period

The intravenous cocaine self-administration model is widely used to characterize the neurobiology of cocaine seeking. When studies are aimed at understanding relapse to cocaine-seeking, a post-cocaine abstinence period is imposed, followed by “relapse” tests to assess the ability of drug-related stimuli (“primes”) to evoke the resumption of the instrumental response previously made to obtain cocaine. Here, we review the literature on the impact of post-cocaine abstinence procedures on neurobiology, finding that the prelimbic and infralimbic regions of the prefrontal cortex are recruited by extinction training, and are not part of the relapse circuitry when extinction training does not occur. Pairing cocaine infusions with discrete cues recruits the involvement of the NA, which together with the dorsal striatum, is a key part of the relapse circuit regardless of abstinence procedures. Differences in molecular adaptations in the NA core include increased expression of GluN1 and glutamate receptor signaling partners after extinction training. AMPA receptors and glutamate transporters are similarly affected by abstinence and extinction. Glutamate receptor antagonists show efficacy at reducing relapse following extinction and abstinence, with a modest increase in efficacy of compounds that restore glutamate homeostasis after extinction training. Imaging studies in humans reveal cocaine-induced adaptations that are similar to those produced after extinction training. Thus, while instrumental extinction training does not have face validity, its use does not produce adaptations distinct from human cocaine users.

Enhancement of the GluN2B subunit of glutamatergic NMDA receptors in rat brain areas after cocaine abstinence

2021 ◽  
pp. 026988112110482
Author(s):  
Irena Smaga ◽  
Karolina Wydra ◽  
Agata Suder ◽  
Marek Sanak ◽  
Lucia Caffino ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Dorsal Hippocampus ◽  
Brain Structures ◽  
Enriched Environment ◽  
Self Administration ◽  
Cocaine Use ◽  
Cocaine Seeking ◽  
Subunit Expression ◽  
Seeking Behavior ◽  
History Of

Background: Cocaine use disorder is associated with compulsive drug-seeking and drug-taking, whereas relapse may be induced by several factors, including stress, drug-related places, people, and cues. Recent observations strongly support the involvement of the N-methyl-D-aspartate (NMDA) receptors in cocaine use disorders and abstinence, whereas withdrawal in different environments may affect the intensification of relapse. Methods: The aim of this study was to examine the GluN2B subunit expression and its association with the postsynaptic density protein 95 (PSD95) in several brain structures in rats with a history of cocaine self-administration and housed either in an enriched environment or in an isolated condition. Furthermore, a selective antagonist of the GluN2B subunit—CP 101,606 (10 and 20 mg/kg) administered during exposure to cocaine or a drug-associated conditional stimulus (a cue) was used to evaluate seeking behavior in rats. Results: In rats previously self-administering cocaine, we observed an increase in the GluN2B expression in the total homogenate from the dorsal hippocampus under both enriched environment and isolation. Cocaine abstinence under isolation conditions increased the GluN2B and GluN2B/PSD95 complex levels in the PSD fraction of the prelimbic cortex in rats previously self-administering cocaine. Administration of CP 101,606 attenuated cue-induced cocaine-seeking behavior only in isolation-housed rats. Conclusion: In summary, in this study we showed region-specific changes in both the expression of GluN2B subunit and NMDA receptor trafficking during cocaine abstinence under different housing conditions. Furthermore, we showed that the pharmacological blockade of the GluN2B subunit may be useful in attenuating cocaine-seeking behavior.

scholarly journals The effect of maternal and post-weaning low and high glycaemic index diets on glucose tolerance, fat deposition and hepatic function in rat offspring

2015 ◽  
Vol 7 (3) ◽  
pp. 320-329 ◽  
Author(s):  
J. Gugusheff ◽  
P. Sim ◽  
A. Kheng ◽  
S. Gentili ◽  
M. Al-Nussairawi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Later Life ◽  
Hepatic Function ◽  
Female Offspring ◽  
Glycaemic Index ◽  
Visceral Adiposity ◽  
Beneficial Effects ◽  
Pregnancy And Lactation ◽  
Total Body ◽  
The Impact

Clinical studies have reported beneficial effects of a maternal low glycaemic index (GI) diet on pregnancy and neonatal outcomes, but the impact of the diet on the offspring in later life, and the mechanisms underlying these effects, remain unclear. In this study, Albino Wistar rats were fed either a low GI (n=14) or high GI (n=14) diet during pregnancy and lactation and their offspring weaned onto either the low or high GI diet. Low GI dams had better glucose tolerance (AUC[glucose], 1322±55 v. 1523±72 mmol min/l, P<0.05) and a lower proportion of visceral fat (19.0±2.9 v. 21.7±3.8% of total body fat, P<0.05) compared to high GI dams. Female offspring of low GI dams had lower visceral adiposity (0.45±0.03 v. 0.53±0.03% body weight, P<0.05) and higher glucose tolerance (AUC[glucose], 1243±29 v. 1351±39 mmol min/l, P<0.05) at weaning, as well as lower hepatic PI3K-p85 mRNA at 12 weeks of age. No differences in glucose tolerance or hepatic gene expression were observed in male offspring, but the male low GI offspring did have reduced hepatic lipid content at weaning. These findings suggest that consuming a low GI diet during pregnancy and lactation can improve glucose tolerance and reduce visceral adiposity in the female offspring at weaning, and may potentially produce long-term reductions in the hepatic lipogenic capacity of these offspring.

scholarly journals Maternal high-fat diet during pregnancy and lactation reduces the appetitive behavioral component in female offspring tested in a brief-access taste procedure

2014 ◽  
Vol 306 (7) ◽  
pp. R499-R509 ◽  
Author(s):  
Yada Treesukosol ◽  
Bo Sun ◽  
Alexander A. Moghadam ◽  
Nu-Chu Liang ◽  
Kellie L. Tamashiro ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
High Fat Diet ◽  
Corn Oil ◽  
Sucrose Concentration ◽  
Maternal Diet ◽  
Female Offspring ◽  
Chow Diet ◽  
High Fat ◽  
Endogenous Opioid ◽  
Pregnancy And Lactation

Maternal high-fat diet appears to disrupt several energy balance mechanisms in offspring. Here, female offspring from dams fed a high-fat diet (HF) did not significantly differ in body weight compared with those fed chow (CHOW), when weaned onto chow diet. Yet when presented with both a chow and a high-fat diet, high-fat intake was significantly higher in HF compared with CHOW offspring. To assess taste-based responsiveness, offspring (12 wk old) were tested in 30-min sessions (10-s trials) to a sucrose concentration series in a brief-access taste test. Compared with CHOW, the HF offspring initiated significantly fewer trials but did not significantly differ in the amount of concentration-dependent licking. Thus, rather than affect lick response (consummatory), maternal diet affects spout approach (appetitive), which may be attributed to motivation-related mechanisms. Consistent with this possibility, naltrexone, an opioid receptor antagonist, further reduced trial initiation, but not licking in both groups. With naltrexone administration, the group difference in trial initiation was no longer evident, suggesting differences in endogenous opioid activity between the two groups. Relative expression of μ-opioid receptor in the ventral tegmental area was significantly lower in HF rats. When trial initiation was not required in one-bottle intake tests, no main effect of maternal diet on the intake of sucrose and corn oil emulsions was observed. Thus, the maternal high-fat diet-induced difference in diet preference is not likely due to changes in the sensory orosensory component of the taste stimulus but may depend on alterations in satiety signals or absorptive mechanisms.

scholarly journals Fos Protein Expression and Cocaine-Seeking Behavior in Rats after Exposure to a Cocaine Self-Administration Environment

2000 ◽  
Vol 20 (2) ◽  
pp. 798-805 ◽  
Author(s):  
Janet L. Neisewander ◽  
David A. Baker ◽  
Rita A. Fuchs ◽  
Ly T. L. Tran-Nguyen ◽  
Art Palmer ◽  
...  
Keyword(s):  
Protein Expression ◽  
Self Administration ◽  
Fos Protein ◽  
Cocaine Seeking ◽  
Seeking Behavior

scholarly journals Prenatal Diet in Relation to Sleep Health of Offspring During Adolescence: Evidence From the ELEMENT Study

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 833-833
Author(s):  
Astrid Zamora ◽  
Karen Peterson ◽  
Martha Maria Téllez-Rojo ◽  
Alejandra Cantoral ◽  
Peter Song ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Maternal Diet ◽  
Principal Component ◽  
Female Offspring ◽  
Sleep Health ◽  
Diet Patterns ◽  
Funding Sources ◽  
Us Epa ◽  
The Mean ◽  
The Impact

Abstract Objectives Maternal diet during gestation has been linked to sex-specific differences in infant sleep; however, the impact on sleep into adolescence is unknown. We sought to examine the relationship between maternal diet patterns and sex-stratified offspring sleep health during adolescence among a Mexico City cohort. Methods Data from 309 mother-adolescent dyads were analyzed. Prenatal diet patterns were formed by principal component analysis derived from a food frequency questionnaire collected over the third trimester. Sleep variables were derived from 7-day actigraphy data from adolescents aged 9–17 years. Linear regression was employed to examine sex-stratified associations between tertiles of the diet patterns with adolescent sleep, adjusting for confounding factors. Results Three diet patterns included: the Prudent Diet (PD), high in lean proteins and vegetables; the Transitioning Mexican Diet (TMD) high in Mexican and “Westernized” foods; and the High Meat & Fat Diet (HMFD), high in meats and high-fat dairy products. The mean (SD) offspring age was 15.1 (1.9) years, and 52.4% of the sample was female. The mean (SD) sleep duration was 8.4 (1.4) h/night. Adjusted analyses showed an association between PD adherence and earlier sleep midpoint among female offspring, the offspring of mothers in the highest tertile of PD had a 0.70 h (95% CI: −1.2, −0.20; p = 0.01) earlier sleep midpoint (p, trend = 0.01). Additional associations were detected between TMD prenatal adherence with shorter sleep duration and earlier sleep midpoint among both sexes. For example, female and male offspring of mothers in the highest tertile of TMD had 0.80 h (95% CI: −85.0, −10.6; p = 0.01) (p, trend = 0.0043) and 0.54 h (95% CI: −66.1, 1.3) (p, trend = 0.03) shorter sleep duration, respectively. HMFD prenatal adherence was associated with less fragmented sleep in a non-linear manner among females and was non-linearly associated with an earlier sleep midpoint among males. Conclusions Sex-stratified analyses demonstrated that findings were more robust between multiple diet patterns and shorter sleep, earlier sleep timing, and less fragmented sleep among female offspring, thus indicating that maternal diet during pregnancy may impact female offspring's sleep health in adolescence. Funding Sources US EPA, NIEHS, NHLBI, and the National Institute of Public Health/Ministry of Health of Mexico.

scholarly journals Disrupting Reconsolidation by Systemic Inhibition of mTOR Kinase via Rapamycin Reduces Cocaine-Seeking Behavior

2021 ◽  
Vol 12 ◽  
Author(s):  
Fushen Zhang ◽  
Shihao Huang ◽  
Haiyan Bu ◽  
Yu Zhou ◽  
Lixiang Chen ◽  
...  
Keyword(s):  
Spontaneous Recovery ◽  
Time Window ◽  
Mammalian Target Of Rapamycin ◽  
Self Administration ◽  
Mtor Inhibition ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
Previously Treated ◽  
Cocaine Infusion ◽  
Paired Tone

Drug addiction is considered maladaptive learning, and drug-related memories aroused by the presence of drug related stimuli (drug context or drug-associated cues) promote recurring craving and reinstatement of drug seeking. The mammalian target of rapamycin signaling pathway is involved in reconsolidation of drug memories in conditioned place preference and alcohol self-administration (SA) paradigms. Here, we explored the effect of mTOR inhibition on reconsolidation of addiction memory using cocaine self-administration paradigm. Rats received intravenous cocaine self-administration training for 10 consecutive days, during which a light/tone conditioned stimulus was paired with each cocaine infusion. After acquisition of the stable cocaine self-administration behaviors, rats were subjected to nosepoke extinction (11 days) to extinguish their behaviors, and then received a 15 min retrieval trial with or without the cocaine-paired tone/light cue delivery or without. Immediately or 6 h after the retrieval trial, rapamycin (10 mg/kg) was administered intraperitoneally. Finally, cue-induced reinstatement, cocaine-priming-induced reinstatement and spontaneous recovery of cocaine-seeking behaviors were assessed in rapamycin previously treated animals, respectively. We found that rapamycin treatment immediately after a retrieval trial decreased subsequent reinstatement of cocaine seeking induced by cues or cocaine itself, and these effects lasted at least for 28 days. In contrast, delayed intraperitoneal injection of rapamycin 6 h after retrieval or rapamycin injection without retrieval had no effects on cocaine-seeking behaviors. These findings indicated that mTOR inhibition within the reconsolidation time-window impairs the reconsolidation of cocaine associated memory, reduces cocaine-seeking behavior and prevents relapse, and these effects are retrieval-dependent and temporal-specific.

scholarly journals Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self-administration and cocaine-seeking behavior in rats

2012 ◽  
Vol 103 (2) ◽  
pp. 332-337 ◽  
Author(s):  
Christopher D. Schmoutz ◽  
Yanan Zhang ◽  
Scott P. Runyon ◽  
Nicholas E. Goeders
Keyword(s):  
Neuropeptide S ◽  
Self Administration ◽  
Cocaine Seeking ◽  
Seeking Behavior

scholarly journals High Maternal Omega-3 Supplementation Dysregulates Body Weight and Leptin in Newborn Male and Female Rats: Implications for Hypothalamic Developmental Programming

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 89
Author(s):  
Soniya Xavier ◽  
Jasmine Gili ◽  
Peter McGowan ◽  
Simin Younesi ◽  
Paul F. A. Wright ◽  
...  
Keyword(s):  
Maternal Diet ◽  
Female Offspring ◽  
Female Rats ◽  
Omega 3 ◽  
Male And Female ◽  
Offspring Development ◽  
Metabolic Outcomes ◽  
Male And Female Rats ◽  
The Impact

Maternal diet is critical for offspring development and long-term health. Here we investigated the effects of a poor maternal diet pre-conception and during pregnancy on metabolic outcomes and the developing hypothalamus in male and female offspring at birth. We hypothesised that offspring born to dams fed a diet high in fat and sugar (HFSD) peri-pregnancy will have disrupted metabolic outcomes. We also determined if these HFSD-related effects could be reversed by a shift to a healthier diet post-conception, in particular to a diet high in omega-3 polyunsaturated fatty acids (ω3 PUFAs), since ω3 PUFAs are considered essential for normal neurodevelopment. Unexpectedly, our data show that there are minimal negative effects of maternal HFSD on newborn pups. On the other hand, consumption of an ω3-replete diet during pregnancy altered several developmental parameters. As such, pups born to high-ω3-fed dams weighed less for their length, had reduced circulating leptin, and also displayed sex-specific disruption in the expression of hypothalamic neuropeptides. Collectively, our study shows that maternal intake of a diet rich in ω3 PUFAs during pregnancy may be detrimental for some metabolic developmental outcomes in the offspring. These data indicate the importance of a balanced dietary intake in pregnancy and highlight the need for further research into the impact of maternal ω3 intake on offspring development and long-term health.

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