Effects of Risperidone on Learning and Memory in Naive and MK-801-Treated Rats

Abstract

Background/Aims: The aim of this study was to investigate the effects of an atypical antipsychotic risperidone (RIS; 0.06, 0.125 or 0.25 mg/kg, intraperitoneal, i.p.) on learning and memory processes, both in naive and MK-801-treated (0.15 mg/kg, i.p.) rats. Methods: Modified elevated plus maze (mEPM), passive avoidance (PA) and Morris water maze (MWM) tasks were used. Results: In the mEPM test, RIS (0.125 or 0.25 mg/kg) significantly decreased the transfer latency and reversed MK-801-induced prolongation in the transfer latency of rats on the 2nd day. In the PA test, RIS (0.125 or 0.25 mg/kg) slightly decreased step-through latency (retention latency) but this finding did not reach statistical significance in naive rats. RIS had no effect on MK-801-induced reduction of retention latency. In the MWM test, RIS (0.06, 0.125 or 0.25 mg/kg, i.p.) neither affected the time spent in the escape platform quadrant, nor the distance to the platform in naive rats. It (0.125 mg/kg) tended to increase MK-801-induced reduction of time spent in the escape platform quadrant, but this finding was insignificant. RIS (0.125 mg/kg) significantly shortened MK-801-induced elongation in the distance to the platform. RIS had no effect on the swimming speed of the animals. Conclusion: RIS might be effective in treating cognitive dysfunctions associated with schizophrenia.

Measure of anxiety-related behaviors and hippocampal BDNF levels associated to the amnesic effect induced by MK-801 evaluated in the modified elevated plus-maze in rats

“…The experimental room was under controlled temperature (22 ± 2°C) and the behavioral testing was conducted using the mEPM learning test [9,15], the classical elevated plusmaze paradigm [32,33] and the open field test, as previously described [34,35]. All injections were done at a volume of 1 ml/kg and all experiments were performed between 8:00 a.m. and 1:00 pm.…”

“…Learning/memory function assessment was done using the mEPM learning test, which measures spatial long-term memory [9,15]. Transfer latency (TL, the time at which animals move from the open arm to the closed arm) was used as an index of learning and memory processes.…”

“…Therefore, it is now accepted that NMDA antagonists are widely used as animal models of cognitive impairments associated to schizophrenia (CIAS) [7,8]. Several evidences have shown memory-impairing effects induced by MK-801 using the modified elevated plus-maze (mEPM) learning test, a non-sophisticated and straightforward paradigm commonly used in rodents [9][10][11][12][13][14][15]. Indeed, some of these studies also investigated the antipsychotic action on the impairment of memory function induced by MK-801 [10,15].…”

“…Several evidences have shown memory-impairing effects induced by MK-801 using the modified elevated plus-maze (mEPM) learning test, a non-sophisticated and straightforward paradigm commonly used in rodents [9][10][11][12][13][14][15]. Indeed, some of these studies also investigated the antipsychotic action on the impairment of memory function induced by MK-801 [10,15]. As the same paradigm allows the detection of anxiolytic or anxiogenic-like behavioral responses, false positive/negative effects on learning/memory function could be produced and anxiety-related behaviors might mimic or interfere with a cognitive impairment.…”

Lamotrigine, a mood stabilizer, may have beneficial effects on memory acquisition and retrieval in mice

“…We have previously reported that gabapentin, a GABA analogue, enhances cognitive performance in naive mice (Celikyurt et al, 2011a). Also, we have been shown that risperidone augmented learning performance in naive (untreated) and MK-801-treated rats in the mEPM test and reduced the distance to the platform in MK-801-treated rats in the MWM test (Celikyurt et al, 2011b).…”