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 2 consecutive days, followed by a 2-week PCP-free period and then 5 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 N, Semenova S, Markou A. Cognitive-disruptive effects of the psychotomimetic phencyclidine and attenuation by atypical antipsychotic medications in rats. Psychopharmacology (Berl) 2007;193:521-37], 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.

Figure 1

Diagram of experimental design.

Figure 2

Effects of 10 mg/kg/day quetiapine treatment on 5-CSRTT performance under baseline conditions and during repeated PCP administration (n = 10 per group). Premature responses (A), accuracy (B), percent correct responses (C), percent omissions (D), latency to correct response (E), and timeout responses (F) are shown as mean ± SEM. Asterisks indicate statistically significant differences compared with baseline performance (*p < 0.05; **p < 0.01; ***p < 0.001). Dagger indicates a statistically significant Presence of Pump × Pump Content interaction (^†p < 0.05). Dollar sign indicates a statistically significant difference from rats treated with vehicle-containing minipumps (^$p < 0.05). Hash signs indicate a statistically significant difference compared with performance after saline injections (^###p < 0.001). “At” sign indicates a trend toward a significant difference compared with performance after saline injections (^@p < 0.06). Shaded areas indicate the period of pump treatment. ↑ denotes a PCP injection.

Figure 3

Effects of 5 mg/kg/day quetiapine treatment on 5-CSRTT performance under baseline conditions and during repeated PCP administration (n = 10–11 per group). Premature responses (A), accuracy (B), percent correct responses (C), percent omissions (D), latency to correct response (E), and timeout responses (F) are shown as mean + SEM. Asterisks indicate statistically significant differences compared with baseline performance (*p < 0.05). Hash signs indicate a statistically significant difference compared with performance after saline injections (^##p < 0.01; ^###p < 0.001). Shaded areas indicate the period of pump treatment. ↑ denotes a PCP injection.