The putative antipsychotic alstonine reverses social interaction withdrawal in mice

Linck, Viviane de Moura; Herrmann, Ana Paula; Goerck, Greice Catrine; Iwu, Maurice M.; Okunji, Christopher O.; Leal, Mirna Bainy; Elisabetsky, Elaine

doi:10.1016/j.pnpbp.2008.04.013

Cited by 28 publications

(21 citation statements)

References 23 publications

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“…Socially suppressing effects of MK-801 in adolescents seen here are reminiscent of the adolescent-only data of Siviy et al (1995) and Moy et al (2012) in adolescent rats and mice, whereas our adult data replicate reductions in social behaviors reported in adult male rodents following drugs that block the NMDA receptor complex (e.g., MK-801, ketamine; de Moura Linck et al 2008; Gururajan et al 2011; Silvestre et al 1997) and using genetically bred mice (Deutsch et al 2011; Jacome et al 2011; Labrie et al 2008). …”

Section: Discussionsupporting

confidence: 81%

“…Among the critical contributors are the neuropeptides oxytocin and vasopressin (Carter 1998; Domes et al 2007; Donaldson and Young 2008), the opioid receptor systems (i.e., mu and kappa opioid receptors; Trezza et al 2011; Vanderschuren et al 1995; Varlinskaya and Spear 2009), GABA system (Sanders and Shekhar 1995a, b), and the glutamate system (de Moura Linck et al 2008; Deutsch et al 2011; Jacome et al 2011; Snigdha and Neill 2008). Of the three subtypes of receptors for glutamate, the N -methyl-D-aspartate (NMDA) receptor has been most strongly implicated in social behavior (de Moura Linck et al 2008; Silvestre et al 1997; Snigdha and Neill 2008). While substantial work has shown impairments of social behaviors due to NMDA receptor antagonists in adult rats and mice, only a few have examined the role of this receptor system on social behaviors in younger rodents (Moy et al 2012; Siviy et al 1995).…”

Section: Introductionmentioning

confidence: 99%

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The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats

Morales

Spear

2013

Psychopharmacology

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Rationale NMDA antagonists consistently produce social inhibition in adult animals, although effects of these manipulations on social behavior of adolescents are relatively unknown. Objectives The aim of this study was to assess potential age differences in the socially inhibitory effects of the non-competitive NMDA antagonist, MK-801, as well as NR2 subunit selective effects, given the regional and developmental differences that exist for the NR2 subunit during ontogeny. Methods In separate experiments, adolescent and adult male Sprague–Dawley rats were treated acutely with MK-801 (0, 0.05, 0.1, 0.2 mg/kg, i.p.), the NR2A antagonist, PEAQX (2.5, 5, 10, 20 mg/kg, s.c.), or the NR2B antagonist, ifenprodil (1.5, 3, 6, 12 mg/kg, i.p.), 10 min prior to a social interaction test. Results Adolescents required higher doses of MK-801 (0.1 and 0.2 mg/kg) to induce social suppression, whereas adults demonstrated reductions in social activity after all doses. Likewise, adolescents required higher doses of ifenprodil (6 and 12 mg/kg) to produce social inhibitory effects relative to adults (all doses). In contrast, adults were less sensitive to PEAQX than adolescents, with adults showing social inhibition after 20 mg/kg whereas adolescents showed this effect following 10 and 20 mg/kg. Although locomotor activity was generally reduced at both ages by all drugs tested, ANCOVAs using locomotor activity as a covariate revealed similar patterns of social inhibitory effects. Conclusions Adolescents are less sensitive than adults to the disruption of social behavior by NMDA and NR2B-selective receptor antagonism, but not by an NR2A antagonist—age differences that may be related to different subunit expression patterns during development.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats

Morales

Spear

2013

Psychopharmacology

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“…This finding is in agreement with previously reported data (Satow et al, 2009) in which acute treatment of clozapine was found to elevate the social interaction time in ketamine-induced social withdrawal mice. However, haloperidol, a typical antipsychotic drug was unable to reverse NMDA receptor agonists (PCP, and MK801)-induced social withdrawal in mice (Qiao et al, 2001; De Moura Linck et al, 2008). One of the main mechanisms involved to alleviate the negative symptoms of psychosis are mediated through inhibition of 5HT 2A receptors (Cepeda and Levine, 2006; Stone et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Mitragyna speciosa Leaf Extract Exhibits Antipsychotic-Like Effect with the Potential to Alleviate Positive and Negative Symptoms of Psychosis in Mice

et al. 2016

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In this study, we investigated the antipsychotic-like effect of methanolic extract of Mitragyna speciosa leaf (MMS) using in vivo and ex vivo studies. In vivo studies comprised of apomorphine-induced climbing behavior, haloperidol-induced catalepsy, and ketamine-induced social withdrawal tests in mice whereas the ex vivo study was conducted utilizing isolated rat vas deferens preparation. Acute oral administration of MMS (50–500 mg/kg) showed an inverted bell-shaped dose-response in apomorphine-induced cage climbing behavior in mice. The effective inhibitory doses of MMS (75 and 100 mg/kg, p.o.) obtained from the apomorphine study was further tested on haloperidol (subcataleptic dose; 0.1 mg/kg, i.p.)-induced catalepsy in the mouse bar test. MMS (75 and 100 mg/kg, p.o.) significantly potentiated the haloperidol-induced catalepsy in mice. Interestingly, MMS at the same effective doses (75 and 100 mg/kg, p.o.) significantly facilitated the social interaction in ketamine-induced social withdrawal mice. Furthermore, MMS inhibited the dopamine-induced contractile response dose-dependently in the isolated rat vas deferens preparations. In conclusion, this investigation provides first evidence that MMS exhibits antipsychotic-like activity with potential to alleviate positive as well as negative symptoms of psychosis in mice. This study also suggests the antidopaminergic activity of MMS that could be responsible for alleviating positive symptoms of psychosis.

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“…Acute treatment with clozapine (1–3 mg/kg) was found to significantly reverse the MK-801-induced (0.6 mg/kg) reduction in social encounters in male rats (Gururajan et al, 2011). Conversely, clozapine (2 mg/kg) was unable to reverse MK-801-induced (0.3 mg/kg) social deficits in male mice (de Moura Linck et al, 2008). Additionally, subchronic treatment (10 days) with clozapine (0.5 mg/kg) and risperidone (0.2 mg/kg) was found to increase non-aggressive social behaviors following administration of ketamine (30 mg/kg for 5 days), while subchronic haloperidol (0.075 mg/kg) had no effect (Becker and Grecksch, 2004).…”

Section: Social Interactionmentioning

confidence: 96%

“…For instance, acute and subchronic treatment of MK-801 (0.1–0.3 mg/kg) has been shown to reduce social interaction in adult male rats and mice (de Moura Linck et al, 2008; Matsuoka et al, 2008; Rung et al, 2005). Further, acute and subchronic administration of ketamine (7–30 mg/kg) impaired social interaction in adult male rats (Becker et al, 2003; Silvestre et al, 1997; Uribe et al, 2013).…”

Section: Social Interactionmentioning

confidence: 99%

Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia

Wilson¹,

Koenig²

2014

European Neuropsychopharmacology

110

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Negative symptoms (e.g., asociality and anhedonia) are a distinct symptomatic domain that has been found to significantly affect the quality of life in patients diagnosed with schizophrenia. Additionally, the primary negative symptom of asociality (i.e., withdrawal from social contact that derives from indifference or lack of desire to have social contact) is a major contributor to poor psychosocial functioning and has been found to play an important role in the course of the disorder. Nonetheless, the pathophysiology underlying these symptoms is unknown and currently available treatment options (e.g., antipsychotics and cognitive-behavioral therapy) fail to reliably produce efficacious benefits. Utilizing rodent paradigms that measure social behaviors (e.g., social withdrawal) to elucidate the neurobiological substrates that underlie social dysfunction and to identify novel therapeutic targets may be highly informative and useful to understand more about the negative symptoms of schizophrenia. Accordingly, the purpose of this review is to provide an overview of the behavioral tasks for assessing social functioning that may be translationally relevant for investigating negative symptoms associated with schizophrenia.

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The putative antipsychotic alstonine reverses social interaction withdrawal in mice

Cited by 28 publications

References 23 publications

The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats

The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats

Mitragyna speciosa Leaf Extract Exhibits Antipsychotic-Like Effect with the Potential to Alleviate Positive and Negative Symptoms of Psychosis in Mice

Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia

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