Rivastigmine reverses cognitive deficit and acetylcholinesterase activity induced by ketamine in an animal model of schizophrenia

Abstract

Schizophrenia is one of the most disabling mental disorders that affects up to 1 % of the population worldwide. Although the causes of this disorder remain unknown, it has been extensively characterized by a broad range of emotional, ideational and cognitive impairments. Studies indicate that schizophrenia affects neurotransmitters such as dopamine, glutamate and acetylcholine. Recent studies suggest that rivastigmine (an acetylcholinesterase inhibitor) is important to improve the cognitive symptoms of schizophrenia. Therefore, the present study evaluated the protective effect of rivastigmine against the ketamine-induced behavioral (hyperlocomotion and cognitive deficit) and biochemical (increase of acetylcholinesterase activity) changes which characterize an animal model of schizophrenia in rats. Our results indicated that rivastigmine was effective to improve the cognitive deficit in different task (immediate memory, long term memory and short term memory) induced by ketamine in rats. Moreover, we observed that rivastigmina reversed the increase of acetylcholinesterase activity induced by ketamine in the cerebral cortex, hippocampus and striatum. However, rivastigmine was not able to prevent the ketamine-induced hyperlocomotion. In conslusion, ours results indicate that cholinergic system might be an important therapeutic target in the physiopathology of schizophrenia, mainly in the cognition, but additional studies should be carried.

The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine

“…Taken together, our results indicate that the administration of AA prevented the positive symptoms of SZ, and was also able to reduce the activity of AChE observed in the animal model, thereby allowing the possible increase in levels of ACh seen in the synaptic cleft. These results corroborate the findings of Zugno et al (2013). This data shows that Ket induced dysfunction of the cholinergic system in the same ways that have been observed in schizophrenic patients.…”

“…In our animals, we observed an increase in the levels of locomotor activity induced by Ket, which was considered an altered behavior related to positive symptoms in an animal model of SZ (Gamma et al 2012, Zugno et al 2013. Krystal et al (1994) also observed similar behavior in humans undergoing subanesthetic doses of Ket.…”

“…This data shows that Ket induced dysfunction of the cholinergic system in the same ways that have been observed in schizophrenic patients. AA can interfere with synaptic plasticity by improving neuronal signaling via its actions within important cellular processes and also due to its antioxidant function, thus acting against the cellular damage caused by Reactive Oxigen species (ROS) (Zugno et al 2013). Arvindakshan et al (2003) demonstrated that there was a significant reduction in the clinical signs of SZ and an increase in the quality of life of schizophrenic patients that were supplemented with AA combined with D-tocopherol and omega 3 twice a day for a period of 4 months.…”

Neurosystems: brain rhythms and cognitive processing

“…MSNs are modulated by both dopamine and acetylcholine (Kreitzer, ), suggesting that the beta oscillation can be upregulated or downregulated, depending on the levels of these two prominent neuromodulators within the striatum. As beta rhythms are involved in cognitive function, it is particularly noteworthy that cognitive function is altered by many of the neuromodulators that affect, directly and/or indirectly, the MSNs of the striatum, including – dopamine (Jaber et al ., ), acetylcholine (Zugno et al ., ), opioids (Iordanova et al ., ), β‐adrenergic agonists (Beversdorf et al ., ), and somatostatin (Tuboly & Vécsei, ).…”

New hypothesis and treatment targets of depression: an integrated view of key findings

“…Furthermore, NMDAR antagonists including ketamine enhance the activity of acetylcholinesterase, thereby promoting the degradation of acetylcholine and leading to cognitive disorders [64] .…”