Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat

A preliminary investigation into the effects of antipsychotics on sub-chronic phencyclidine-induced deficits in attentional set-shifting in female rats

“…However, there is evidence that the dosing schedule used here produces robust deficits in female rats as we have demonstrated long-term deficits in reversal learning [2,3], NOR performance [22] and now attentional set-shifting in addition to neurobiological changes of relevance to schizophrenia such as reduced parvalbumin and BDNF [3,53]. These PCP-induced behavioural deficits in reversal learning and NOR are improved by atypical but not classical antipsychotics [2,22,42].…”

“…The use of only one dose of antipsychotics is another limitation, a dose response should ideally have been conducted; however, in order to limit the number of animals used, and length of testing, we carefully selected one active dose of each antipsychotic. The doses of clozapine and risperidone were chosen on the basis of our previous work showing efficacy against sub-chronic PCP-induced deficits in reversal learning [2,42] and NOR [22]. The dose of haloperidol was chosen on the basis of our previous work showing that 0.05 mg/kg haloperidol significantly attenuated a d-amphetamine-induced reversal learning impairment in female hooded-Lister rats [28].…”

“…Indeed, in our laboratory, administration of sub-chronic PCP to female rats (2 mg/kg twice daily for 7 days followed by 7 days drug free) produces deficits in reversal learning, attenuated by atypical but not classical antipsychotics [2]. Recently we have found that sub-chronic PCP-induced deficits in NOR are reversed by acute clozapine and risperidone, but not haloperidol [22]. Rodefer and colleagues combined the attentional set-shifting test with a sub-chronic dosage regimen (5 mg/kg twice daily for seven days followed by a ten-day drug washout period) and found a selective deficit in the EDS phase [49].…”

“…Furthermore, this dose of haloperidol has been shown to occupy 50% of dopamine D 2 receptors [34,35]. The doses of clozapine and risperidone were chosen on the basis of our previous work showing efficacy against sub-chronic PCP in the reversal learning paradigm [2,42] and NOR task [22]. PCP HCl (Sigma, UK) was dissolved in 0.9% saline.…”

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

“…In our laboratory, we have shown that PCP selectively impairs performance in reversal learning (Abdul-Monim et al, 2006;McLean et al, 2009), attentional set-shifting (McLean et al, 2008a) and novel object recognition (Grayson et al, 2007), importantly these tests are all of relevance to schizophrenia as highlighted by the MATRICS.ucla.edu initiative (Measurement and Treatment Research to Improve Cognition in Schizophrenia), and subsequently the TURNS.ucla.edu program (Treatment Units for Research on Neurocognition and Schizophrenia). Our sub-chronic PCP dosing regime causes reduced density of parvalbumin-immunoreactive neurons in hippocampal regions (Abdul-Monim et al, 2007) and levels of brain-derived neurotrophic factor mRNA (BDNF) in cortical regions (Snigdha et al, 2007) in rats.…”