Altered adult locomotor activity in rats from phencyclidine treatment on postnatal days 7, 9 and 11, but not repeated ketamine treatment on postnatal day 7

The dopamine D 3 -preferring D 2 /D 3 dopamine receptor partial agonist, cariprazine, reverses behavioural changes in a rat neurodevelopmental model for schizophrenia

“…While neonatal PCP alone does not induce hyperlocomotion (Boctor and Ferguson, 2010) this is a consistent trait of social isolation attenuated by a range of antipsychotics, including haloperidol, risperidone and olanzapine (Fabricius et al, 2011; McIntosh et al, 2013). As hyperlocomotion probably results from increased mesolimbic dopamine, thought to contribute to positive symptoms of schizophrenia (Fone and Porkess, 2008), its attenuation herein supports the potential antipsychotic properties of cariprazine.…”

“…Of particular note, cariprazine produced a dose-related reversal of the PCP-induced impairment of social recognition memory and delayed T-maze alternation in wild type mice but was unable to reverse these deficits in D3 receptor knockout mice (Zimnisky et al, 2013), consistent with the idea that partial agonist activity at this receptor may play an important contribution to this pro-cognitive effect in social recognition and spatial working memory. It would be valuable to assess the impact of cariprazine on PCP-isolation-induced impairments of other cognitive domains relevant to those impaired in schizophrenia, such as social cognition in future studies.Combined neonatal PCP and isolation caused the expected hyperactivity in a novel arena and during social interaction which was significantly reduced by cariprazine or aripiprazole.While neonatal PCP alone does not induce hyperlocomotion (Boctor and Ferguson, 2010) this is a consistent trait of social isolation attenuated by a range of antipsychotics, including haloperidol, risperidone and olanzapine (Fabricius et al, 2011; McIntosh et al, 2013). As hyperlocomotion probably results from increased mesolimbic dopamine, thought to contribute to positive symptoms of schizophrenia (Fone and Porkess, 2008), its attenuation herein supports the potential antipsychotic properties of cariprazine.…”

Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment

“…Similar to that previously described for rats [32], a push-pull strain gauge apparatus (Chatillon Model DPP, San Diego Instruments, San Diego, CA) was used to measure kilogram of force. The tester allowed the forelimbs of the mouse to grasp a triangular bar after which the mouse's body was quickly pulled away.…”

GABAA overactivation potentiates the effects of NMDA blockade during the brain growth spurt in eliciting locomotor hyperactivity in juvenile mice

“…However, the fact that locomotor hyperactivity was observed only in MK-801-treated mice suggests that, during the brain growth spurt, the blockade of NMDA receptors is more important than the hyperactivation of GABAA receptors in eliciting juvenile locomotor hyperactivity. Accordingly, increased locomotor activity has been described in juvenile rats after the treatment with MK-801 from PND6 to PND21 (Schiffelholz et al, 2004), from PND7 to PND10 (Kocahan et al, 2013) and from PND1 to PND20 (Facchinetti et al, 1993), as well as after the administration of other NMDAR antagonists during the brain growth spurt (Boctor and Ferguson, 2010;Fredriksson and Archer, 2003). The absence of locomotor hyperactivity in mice treated with muscimol is in line with the finding that muscimol exposure at PND1 and PND2 did not affect spontaneous locomotor activity of juvenile rats in an open field test (Nunez et al, 2003).…”