Increased impulsivity and disrupted attention induced by repeated phencyclidine are not attenuated by chronic quetiapine treatment

Abstract

Atypical antipsychotic medications differ in how effectively they attenuate cognitive and other deficits in schizophrenia. The present study aimed to explore whether quetiapine, an atypical antipsychotic medication, would reverse disruptions of performance in the 5-choice serial reaction time task (5-CSRTT), a test of attention and impulsivity, induced by repeated administration of the psychotomimetic phencyclidine (PCP). In confirmation of previous findings, repeated PCP administration (2 mg/kg, s.c., 30 min before behavioral testing, for two consecutive days, followed by a 2-week PCP-free period and then five consecutive days of PCP treatment) increased premature responding (impulsivity), decreased accuracy (attention), and increased response latencies (processing speed) and timeout responding (impulsivity/cognitive inflexibility). Chronic quetiapine (5 or 10 mg/kg/day, s.c.) did not attenuate these PCP-induced disruptions in performance, while at the highest dose used, quetiapine disrupted 5-CSRTT performance in the absence of PCP treatment and tended to exacerbate the PCP-induced increase in premature responding. Considering that clozapine, another atypical antipsychotic, was shown previously to reverse PCP-induced deficits in the same task (Amitai et al. 2007), the present findings demonstrate differences between clozapine and quetiapine in their effectiveness on schizophrenia-like cognitive deficits and impulsivity that may be attributable to their different receptor affinity profiles.

Dissociation of acute and chronic intermittent phencyclidine-induced performance deficits in the 5-choice serial reaction time task: influence of clozapine

“…This is consistent with the results of Amitai and Markou (2009). This continuation of a behavioural response may be considered to be related to perseveration which is a form of cognitive inflexibility.…”

“…Under these conditions PCP treatment increases impulsivity in the 5-CSRTT and this deficit is partially reversed by clozapine but not by quetiapine (Le Pen et al 2003;Amitai et al 2007;Amitai and Markou 2009). Whilst these studies demonstrate the immediate consequences of NMDA receptor blockade upon behavioural responding, perhaps coinciding with an 'acute psychotic episode' they do not illuminate upon the chronic and persistent effects of PCP that may mirror the chronic enduring deficit state of the illness.…”

Caution When Diagnosing Your Mouse With Schizophrenia: The Use and Misuse of Model Animals for Understanding Psychiatric Disorders

“…(78). When tested in a battery of behavioral assays, these mice showed hyperactivity in a locomotor test, mildly disrupted prepulse inhibition (at one prepulse intensity only), and increased immobility in the forced swim test but no change in open field or plus maze tests, spontaneous alternation in a Y-maze, social interaction test, or spatial memory as assessed in a water maze test (79).…”

Dyskinesias and impulse control disorders in Parkinson's disease: From pathogenesis to potential therapeutic approaches

“…Pharmacology Dyskinesia Impulsivity and addictions Dopaminergic and/or serotonergic system Sarizotan D2-like receptor antagonist and 5-HT 1A agonist in 6-OHDA rat and MPTP monkey (Grégoire et al, 2009;Marin et al, 2009) Buspirone 5-HT 1A partial agonist and D2-like receptor antagonist in 6-OHDA and MPTP rodents (Dupre et al, 2007(Dupre et al, , 2008Eskow et al, 2007Eskow et al, , 2009Kannari et al, 2001;Lundblad et al, 2005;Tomiyama et al, 2005) impulsivity after acute treatment and impulsivity after chronic treatment in rat (Lu et al, 2013) methamphetamine and cocaine reinstatement in rat (Shelton et al, 2013) Tandospirone 5-HT 1A partial agonist impulsive choice in rat (Ohmura et al, 2013) Quetiapine 5-HT 2A antagonist, D2-like receptor antagonist, adrenergic antagonist in 6-OHDA rat and MPTP monkey (Oh et al, 2002) impulsivity at a high dose in rat (Amitai and Markou, 2009 Non-selective opioid receptor antagonist suppresses ethanol-induced behaviors in alcohol preferring rat (June et al, 2004) GABAergic system Topiramate GABA A agonist in MPTP monkey (Silverdale et al, 2005) and synergistic effect with amantadine in 6-OHDA rat (Kobylecki et al, 2011) Voluntary alcohol intake in alcohol high preferring rats (Johnston et al, 2010;Savola et al, 2003) Propanolol ␤1/␤2 receptors antagonist in 6-OHDA rat and MPTP monkey (Dekundy et al, 2007;Gomez-Mancilla and Bedard, 1993) different substances induced abnormal behaviors (impulsivity, conditioned place preference. .…”