Oxytocin modulates psychotomimetic-induced deficits in sensorimotor gating

Feifel, David; Reza, Tammi

doi:10.1007/s002130050811

Cited by 111 publications

(93 citation statements)

References 36 publications

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“…Our results are consistent with a study in rats demonstrating PCPinduced disruptions of PPI can be ameliorated by pretreatment with Oxt. 27 They also found that Oxt pretreatment reduced the effects of Amp, but not Apo, on disrupted PPI. 27 The lack of genotypic effect observed following treatment with Amp or Apo suggests that the dopaminergic system, involved in the regulation of PPI, is less affected, if not normal, in OxtÀ/À mice.…”

Section: Discussionmentioning

confidence: 95%

“…Also in rats, pharma-cologically disrupted PPI can be restored with Oxt administration. 27 Consequently, it has been hypothesized that Oxt may act as an endogenous antipsychotic. 27,28 In 'normal' animals, PPI is disrupted by the administration of drugs such as apomorphine (Apo) that acts as an agonist at D1 and D2 family dopamine receptors and amphetamine (Amp) that releases and inhibits reuptake of dopamine, 29,30 as well as the noncompetitive N-methyl-D-aspartic acid (NMDA)/ glutamate receptor antagonist phencyclidine (PCP).…”

Section: Introductionmentioning

confidence: 99%

“…27 Consequently, it has been hypothesized that Oxt may act as an endogenous antipsychotic. 27,28 In 'normal' animals, PPI is disrupted by the administration of drugs such as apomorphine (Apo) that acts as an agonist at D1 and D2 family dopamine receptors and amphetamine (Amp) that releases and inhibits reuptake of dopamine, 29,30 as well as the noncompetitive N-methyl-D-aspartic acid (NMDA)/ glutamate receptor antagonist phencyclidine (PCP). 29,31 The availability of Oxt knockout (À/À) mice provided an opportunity to assess, in the PPI model, the hypothesis that Oxt can act as a 'natural' antipsychotic.…”

Section: Introductionmentioning

confidence: 99%

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Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

2008

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It has been previously suggested that oxytocin (Oxt) may act as a natural antipsychotic. To test this hypothesis, we investigated whether disruption of the oxytocin gene (OxtÀ/À) made mice more susceptible to the psychosis-related effects of amphetamine (Amp), apomorphine (Apo) and phencyclidine (PCP). We examined drug-induced changes in the prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating deficits characteristic of several psychiatric and neurological disorders, including schizophrenia. We found that treatment with Amp, Apo and PCP all had effects on PPI. However, in OxtÀ/À mice, but not Oxt þ / þ mice, PCP treatment resulted in large PPI deficits. As PCP is a noncompetitive N-methyl-D-aspartic acid receptor antagonist, these findings suggest that the absence of Oxt alters the glutamatergic component of the PPI.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

2008

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“…Whereas all antipsychotics tested can block amphetamine-induced disruption of PPI, only some drugs can block the PPI effects of non-competitive NMDA antagonists. These include several atypical antipsychotics (Bakshi and Geyer, 1995;Bakshi et al 1994;Swerdlow et al 1996), serotonin (Varty and Higgins 1995), alphaadrenergic antagonists (Bakshi and Geyer 1997), nitric oxide synthetase inhibitors , and some neuropeptides (Feifel and Reza 1999;Feifel et al 1999b). Thus, OLETF rats may have alterations in one or more of these systems making them less sensitive to the PPI disrupting effects of non-competitive NMDA antagonists.…”

Section: Discussionmentioning

confidence: 99%

Startle and Sensorimotor Gating in Rats Lacking CCK-A Receptors

Feifel

2001

Neuropsychopharmacology

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Long Evans Tokushima Fatty (OLETF) rats lack CCK-A receptors because of a genetic mutation. Previous studies have shown that CCK-A receptors seem to play a role in the regulation of prepulse inhibition (PPI) of the startle reflex, an operational measure of sensorimotor gating. This study investigated baseline and drug-disrupted PPI in OLETF rats and their non-mutant counterparts, Long Evans Tokushima Otsuka (LETO) rats. Baseline PPI did not differ significantly between the two rat genotypes but OLETF rats exhibited a higher acoustic startle response compared to LETO rats. Amphetamine (2 mg/kg), and the dizocilpine (0.1 mg/ kg), disrupted PPI in LETO rats but not in the OLETF rats. Apomorphine (0.5 mg/kg) failed to disrupt PPI in both LETO and OLETF rats, and haloperidol (0.5 Cholecystokinin (CCK), a gut-brain peptide, has been implicated in the modulation of mesolimbic dopamine transmission. CCK coexists with dopamine in a large proportion of mesolimbic neurons that terminate in the medial-posterior nucleus accumbens (mpNAC) (Hokfelt et al. 1980). CCK co-localized in mesolimbic dopamine cells appears to potentiate dopamine transmission via CCK-A receptors in the mpNAC (Crawley 1991). CCK in the periphery has also been shown to regulate mesolimbic function by what appears to be a presynaptic mechanism of action mediated by peripheral CCK-A receptors (Kariya et al. 1994;Kihara et al. 1993). Because of its ability to regulate mesolimbic function, the CCK-A system could contribute to mechanism underlying psychiatric disorders such as schizophrenia.Otsuka Long Evans Tokushima Fatty (OLETF) rats lack CCK-A receptors because of a spontaneous mutation (Funakoshi et al. 1995). These rats have been studied extensively as a model to understand the metabolic role of peripheral CCK as they have a tendency to demonstrate diabetes-like changes after 18 weeks of age (Otsuki et al. 1995). OLETF rats represent a potentially useful model to investigate the role of the endogenous CCK-A system in the regulation of mesolimbic dopamine function. A previous study found that OLETF rats exhibited decreased spontaneous locomotor activity relative to Long Evans Tokushimo Otsuka (LETO) rats, 24 , NO . 6 their control counterparts, and the authors suggested that this difference may be the result of perturbations in basal dopamine regulation in OLETF rats (Kobayashi et al. 1996). We previously reported that amphetamineinduced early gene expression, as measured by zif 268 mRNA expression in the NAC, did not differ between LETO and OLETF rats (Shilling et al. 2000).To further examine the role of the CCK-A receptor in the regulation of mesolimbic dopamine function, this study investigated prepulse inhibition (PPI) in OLETF and LETO rats. PPI is the normal suppression of the startle response when the intense startling stimulus (pulse) is preceded immediately (50-200 msecs) by a much weaker, non-startling stimulus (prepulse) such as an auditory "click". PPI was studied because it is an operational measure of sensorimotor gating and the ba...

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“…Vasotocin and isotocin are the fish homologues of vasopressin and oxytocin, two nonapeptides closely associated with sociality in mammals (including affiliative and sexual behaviours [32]), plus social/ emotional processing, stress response modulation, learning and memory [33][34][35][36]. Oxytocin has antipsychotic properties [28,37,38] and has been shown to restore deficits in sensorimotor gating induced by MK-801 in rats [39]. The association between MK-801 exposure and isotocin/vasotocin may indicate an unexpected conservation with mammalian patterns in modulating aspects of glutamatergic signalling in fish, and may also reflect molecular stress and coping responses to cognitive disruption [33,34].…”

Section: Discussionmentioning

confidence: 99%

Testing synaptic plasticity in dynamic mate choice decisions: N -methyl d -aspartate receptor blockade disrupts female preference

Ramsey

Cummings

2014

Proc. R. Soc. B.

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Social behaviours such as mate choice require context-specific responses, often with evolutionary consequences. Increasing evidence indicates that the behavioural plasticity associated with mate choice involves learning. For example, poeciliids show age-dependent changes in female preference functions and express synaptic-plasticity-associated molecular markers during mate choice. Here, we test whether social cognition is necessary for female preference behaviour by blocking the central player in synaptic plasticity, NMDAR (N-methyl D-aspartate receptor), in a poeciliid fish, Xiphophorus nigrensis. After subchronic exposure to NMDAR antagonist MK-801, female preference behaviours towards males were dramatically reduced. Overall activity levels were unaffected, but there was a directional shift from 'social' behaviours towards neutral activity. Multivariate gene expression patterns significantly discriminated between females with normal versus disrupted plasticity processes and correlated with preference behaviours-not general activity. Furthermore, molecular patterns support a distinction between 'preference' (e.g. neuroserpin, neuroligin-3, NMDAR) and 'sociality' (isotocin and vasotocin) gene clusters, highlighting a possible conservation between NMDAR disruption and nonapeptides in modulating behaviour. Our results suggest that mate preference may involve greater social memory processing than overall sociality, and that poeciliid preference functions integrate synaptic-plasticity-oriented 'preference' pathways with overall sociality to invoke dynamic, context-specific responses towards favoured males and away from unfavoured males.

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Oxytocin modulates psychotomimetic-induced deficits in sensorimotor gating

Cited by 111 publications

References 36 publications

Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

Startle and Sensorimotor Gating in Rats Lacking CCK-A Receptors

Testing synaptic plasticity in dynamic mate choice decisions: N -methyl d -aspartate receptor blockade disrupts female preference

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