Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice

Kuteykin-Teplyakov, Konstantin; Maldonado, Rafaël

doi:10.1016/j.euroneuro.2014.08.007

Cited by 14 publications

(8 citation statements)

References 49 publications

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“…The 5-HT 1A antagonist WAY 100,635 reduces the increase in plasma OT levels and the adjacent lying behavior of rats induced by MDMA ( 88 ). In line with this, the selective OT receptor antagonist L-3668999 abolishes the prosocial effects of MDMA in mice, and quantitative analyses of brain proteome have revealed changes in 21 proteins associated with sociability ( 89 ). In addition, the MDMA-induced increase in rodent prosocial behavior is prevented by the same dose of WAY 100,635 and the 5-HT 2B / 2C receptor antagonist SB 206553 ( 90 ), thus suggesting that the prosocial effect of MDMA in rodents may be mediated by OT release as a result of 5-HT 1A and 5-HT 2B/2C receptor interactions.…”

Section: Discussionmentioning

confidence: 77%

The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish

et al. 2017

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3,4-Methylenedioxymethamphetamine (MDMA) and its derivatives, 2,5-dimethoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA), are recreational drugs whose pharmacological effects have recently been attributed to serotonin 5HT2A/C receptors. However, there is growing evidence that the oxytocin (OT)/vasopressin system can modulate some the effects of MDMA. In this study, MDMA (2.5–10 mg/kg), DOB (0.5 mg/kg), or PMA (0.005, 0.1, or 0.25 mg/kg) were administered intramuscularly to adult zebra fish, alone or in combination with the V1a vasopressin antagonist, SR49059 (0.01–1 ng/kg), before carrying out conditioned place preference (CPP), social preference, novel tank diving, and light–dark tests in order to evaluate subsequent rewarding, social, and emotional-like behavior. The combination of SR49059 and each drug progressively blocked: (1) rewarding behavior as measured by CPP in terms of time spent in drug-paired compartment; (2) prosocial effects measured on the basis of the time spent in the proximity of a nacre fish picture; and (3) anxiolytic effects in terms of the time spent in the upper half of the novel tank and in the white compartment of the tank used for the light–dark test. Antagonism was obtained at SR49059 doses which, when given alone, did not change motor function. In comparison with a control group, receiving vehicle alone, there was a three to five times increase in the brain release of isotocin (the analog of OT in fish) after treatment with the most active doses of MDMA (10 mg/kg), DOB (0.5 mg/kg), and PMA (0.1 mg/kg) as evaluated by means of bioanalytical reversed-phase high-performance liquid chromatography. Taken together, these findings show that the OT/vasopressin system is involved in the rewarding, prosocial, and anxiolytic effects of MDMA, DOB, and PMA in zebra fish and underline the association between this system and the behavioral alterations associated with disorders related to substance abuse.

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Section: Discussionmentioning

confidence: 77%

The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish

et al. 2017

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“…The prosocial effects of SR -MDMA have been extensively studied in humans (Kamilar-Britt and Bedi, 2015), and similar effects have been observed in rodents, with SR -MDMA increasing social interaction (Morley and McGregor, 2000) and preference for social contexts (Kuteykin-teplyakov and Maldonado, 2014). However, the prosocial effects of MDMA’s enantiomers have not been previously studied in rodents.…”

Section: Discussionmentioning

confidence: 79%

Separating the agony from ecstasy: R(–)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice

et al. 2018

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S,R(+/-)-3,4-methylenedioxymethamphetamine (SR-MDMA) is an amphetamine derivative with prosocial and putative therapeutic effects. Ongoing clinical trials are investigating it as a treatment for post-traumatic stress disorder (PTSD) and other conditions. However, its potential for adverse effects such as hyperthermia and neurotoxicity may limit its clinical viability. We investigated the hypothesis that one of the two enantiomers of SR-MDMA, R-MDMA, would retain the prosocial and therapeutic effects but with fewer adverse effects. Using male Swiss Webster and C57BL/6 mice, the prosocial effects of R-MDMA were measured using a social interaction test, and the therapeutic-like effects were assessed using a Pavlovian fear conditioning and extinction paradigm relevant to PTSD. Locomotor activity and body temperature were tracked after administration, and neurotoxicity was evaluated post-mortem. R-MDMA significantly increased murine social interaction and facilitated extinction of conditioned freezing. Yet, unlike racemic MDMA, it did not increase locomotor activity, produce signs of neurotoxicity, or increase body temperature. A key pharmacological difference between R-MDMA and racemic MDMA is that R-MDMA has much lower potency as a dopamine releaser. Pretreatment with a selective dopamine D1 receptor antagonist prevented SR-MDMA-induced hyperthermia, suggesting that differential dopamine signaling may explain some of the observed differences between the treatments. Together, these results indicate that the prosocial and therapeutic effects of SR-MDMA may be separable from the stimulant, thermogenic, and potential neurotoxic effects. To what extent these findings translate to humans will require further investigation, but these data suggest that R-MDMA could be a more viable therapeutic option for the treatment of PTSD and other disorders for which SR-MDMA is currently being investigated.

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“…Finally, to investigate whether exogenous oxytocin administration was exerting its effects on ethanol consumption in the DID model via actions at the oxytocin receptor, a separate cohort of mice (n= 40) was pretreated with the selective brain penetrant, nonpeptide oxytocin receptor antagonist L-368,899 (10 mg/kg) (Borthwick, 2010; Kuteykin-Teplyakov and Maldonado, 2014; Olszewski et al, 2013) or vehicle (0.9% saline) 15 min prior to OT (1 mg/kg) or vehicle (saline) administration (ip. ), which was given 30 min before the start of the 4-hr test drinking session.…”

Section: Methodsmentioning

confidence: 99%

Oxytocin Reduces Ethanol Self‐Administration in Mice

King

Griffin

Luderman

et al. 2017

Alcoholism Clin & Exp Res

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Background Excessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption. Methods Male C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking (“drinking-in-the-dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, ethanol (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive- ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Results Oxytocin (0, 0.3, 1, 3 or 10mg/kg) dose-dependently reduced ethanol consumption (maximal 45% reducton) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin’s effect was blocked by pretreatment with an oxytocin receptor antagonist and the pattern of contacts (licks) at the ethanol bottle suggested a reduction in motivation to drink ethanol. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for ethanol and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for ethanol at doses that did not alter responding for sucrose. Discussion These results indicate that oxytocin reduces ethanol consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for ethanol at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Neverthess, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder.

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Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice

Cited by 14 publications

References 49 publications

The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish

The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish

Separating the agony from ecstasy: R(–)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice

Oxytocin Reduces Ethanol Self‐Administration in Mice

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