Antiaggressive Activity of Central Oxytocin in Male Rats.

Antiaggressive activity of central oxytocin in male rats.

Psychopharmacology (Berl). 2013 Apr 28;
Calcagnoli F, de Boer SF, Althaus M, den Boer JA, Koolhaas JM

RATIONALE: A substantial body of research suggests that the neuropeptide oxytocin promotes social affiliative behaviors in a wide range of animals including humans. However, its antiaggressive action has not been unequivocally demonstrated in male laboratory rodents. OBJECTIVE: Our primary goal was to examine the putative serenic effect of oxytocin in a feral strain (wild type Groningen, WTG) of rats that generally show a much broader variation and higher levels of intermale aggression than commonly used laboratory strains of rats. METHODS: Resident animals were intracerebroventricularly (icv) administered with different doses of synthetic oxytocin and oxytocin receptor antagonist, alone and in combination, in order to manipulate brain oxytocin functioning and to assess their behavioral response to an intruder. RESULTS: Our data clearly demonstrate that acute icv administered oxytocin produces dose-dependent and receptor-selective changes in social behavior, reducing aggression and potentiating social exploration. These antiaggressive effects are stronger in the more offensive rats. On the other hand, administration of an oxytocin receptor antagonist tends to increase (nonsignificantly) aggression only in low-medium aggressive animals. CONCLUSIONS: These results suggest that transiently enhancing brain oxytocin function has potent antiaggressive effects, whereas its attenuation tends to enhance aggressiveness. In addition, a possible inverse relationship between trait aggression and endogenous oxytocinergic signaling is revealed. Overall, this study emphasizes the importance of brain oxytocinergic signaling for regulating intermale offensive aggression. This study supports the suggestion that oxytocin receptor agonists could clinically be useful for curbing heightened aggression seen in a range of neuropsychiatric disorders like antisocial personality disorder, autism, and addiction. HubMed – addiction


Early Adolescent Growth in Depression and Conduct Problem Symptoms as Predictors of Later Substance Use Impairment.

J Abnorm Child Psychol. 2013 Apr 28;
McCarty CA, Wymbs BT, Mason WA, King KM, McCauley E, Baer J, Vander Stoep A

Most studies of adolescent substance use and psychological comorbidity have examined the contributions of conduct problems and depressive symptoms measured only at particular points-in-time. Yet, during adolescence, risk factors such as conduct problems and depression exist within a developmental context, and vary over time. Though internalizing and comorbid pathways to substance use have been theorized (Hussong et al. Psychology of Addictive Behaviors 25:390-404, 2011), the degree to which developmental increases in depressive symptoms and conduct problems elevate risk for substance use impairment among adolescents, in either an additive or potentially a synergistic fashion, is unclear. Using a school-based sample of 521 adolescents, we tested additive and synergistic influences of changes in depressive symptoms and conduct problems from 6th to 9th grade using parallel process growth curve modeling with latent interactions in the prediction of late adolescent (12th grade) substance use impairment, while examining gender as a moderator. We found that the interaction between growth in depression and conduct disorder symptoms uniquely predicted later substance use problems, in addition to main effects of each, across boys and girls. Results indicated that adolescents whose parents reported increases in both depression and conduct disorder symptoms from 6th to 9th grade reported the most substance use-related impairment in 12th grade. The current study demonstrates that patterns of depression and conduct problems (e.g., growth vs. decreasing) are likely more important than the static levels at any particular point-in-time in relation to substance use risk. HubMed – addiction


The mGluR2/3 agonist LY379268 induced anti-reinstatement effects in rats exhibiting addiction-like behavior.

Neuropsychopharmacology. 2013 Apr 29;
Cannella N, Halbout B, Uhrig S, Evrard L, Corsi M, Corti C, Deroche-Gamonet V, Hansson AC, Spanagel R

Medication development for cocaine-addicted patients is difficult, and many promising preclinical candidates have failed in clinical trials. One reason for the difficulty in translating preclinical findings to the human condition is that drug testing is typically conducted in behavioral procedures in which animals do not show addiction-like traits. Recently, a DSM-IV-based animal model has been developed that allows studying the transition to an addiction-like behavior. Changes in synaptic plasticity are involved in the transition to cocaine addiction. In particular, it has been shown that metabotropic glutamate receptor 2/3 (mGluR2/3)-mediated long-term depression is suppressed in the prelimbic cortex in addict-like rats. We therefore hypothesized that cocaine-seeking in addict-like rats could be treated with an mGluR2/3 agonist. Indeed, addict-like rats that were treated systemically with the mGluR2/3 agonist LY379268 (0, 0.3, 3?mg/kg) showed a pronounced reduction in cue-induced reinstatement of cocaine-seeking. In an attempt to dissect the role played by mGluR2 and mGluR3 in cue-induced reinstatement, we analyzed the mRNA expression patterns in several relevant brain areas but did not find any significant differences between cocaine addict-like and non-addict-like rats, suggesting that the behavioral differences observed are due to translational rather than transcriptional regulation. Another possibility to study the contributions of mGluR2 and mGluR3 in mediating addictive-like behavior is the use of knockout models. Because mGluR2 knockouts cannot be used in operant procedures due to motoric impairment, we only tested mGluR3 knockouts. These mice did not differ from controls in reinstatement, suggesting that mGluR2 receptors are critical in mediating addictive-like behavior.Neuropsychopharmacology accepted article preview online, 29 April 2013; doi:10.1038/npp.2013.106. HubMed – addiction



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