PMID- 31945381 OWN - NLM STAT- MEDLINE DCOM- 20210107 LR - 20231213 IS - 1873-5177 (Electronic) IS - 0091-3057 (Linking) VI - 189 DP - 2020 Feb TI - Chronic oral treatment with risperidone impairs recognition memory and alters brain-derived neurotrophic factor and related signaling molecules in rats. PG - 172853 LID - S0091-3057(19)30470-8 [pii] LID - 10.1016/j.pbb.2020.172853 [doi] AB - Antipsychotic drugs (APDs) are essential for the treatment of schizophrenia and other neuropsychiatric illnesses such as bipolar disease. However, they are also extensively prescribed off-label for many other conditions, a practice that is controversial given their potential for long-term side effects. There is clinical and preclinical evidence that chronic treatment with some APDs may lead to impairments in cognition and decreases in brain volume, although the molecular mechanisms of these effects are unknown. The purpose of the rodent studies described here was to evaluate a commonly prescribed APD, risperidone, for chronic effects on recognition memory, brain-derived neurotrophic factor (BDNF), its precursor proBDNF, as well as relevant downstream signaling molecules that are known to influence neuronal plasticity and cognition. Multiple cohorts of adult rats were treated with risperidone (2.5 mg/kg/day) or vehicle (dilute acetic acid solution) in their drinking water for 30 or 90 days. Subjects were then evaluated for drug effects on recognition memory in a spontaneous novel object recognition task and protein levels of BDNF-related signaling molecules in the hippocampus and prefrontal cortex. The results indicated that depending on the treatment period, a therapeutically relevant daily dose of risperidone impaired recognition memory and increased the proBDNF/BDNF ratio in the hippocampus and prefrontal cortex. Risperidone treatment also led to a decrease in Akt and CREB phosphorylation in the prefrontal cortex. These results indicate that chronic treatment with a commonly prescribed APD, risperidone, has the potential to adversely affect recognition memory and neurotrophin-related signaling molecules that support synaptic plasticity and cognitive function. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Poddar, Indrani AU - Poddar I AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America. FAU - Callahan, Patrick M AU - Callahan PM AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.; Small Animal Behavior Core, Augusta University, Augusta, GA 30912, United States of America. FAU - Hernandez, Caterina M AU - Hernandez CM AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America. FAU - Pillai, Anilkumar AU - Pillai A AD - Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America. FAU - Yang, Xiangkun AU - Yang X AD - Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, GA 30607, United States of America. FAU - Bartlett, Michael G AU - Bartlett MG AD - Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, GA 30607, United States of America. FAU - Terry, Alvin V Jr AU - Terry AV Jr AD - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.; Small Animal Behavior Core, Augusta University, Augusta, GA 30912, United States of America. Electronic address: aterry@augusta.edu. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200113 PL - United States TA - Pharmacol Biochem Behav JT - Pharmacology, biochemistry, and behavior JID - 0367050 RN - 0 (Antipsychotic Agents) RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, rat) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Nerve Growth Factors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - L6UH7ZF8HC (Risperidone) SB - IM MH - Administration, Oral MH - Animals MH - Antipsychotic Agents/*administration & dosage/blood/*pharmacology MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Catalepsy/chemically induced/diagnosis MH - Cognition/drug effects MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Hippocampus/metabolism MH - Male MH - Nerve Growth Factors/metabolism MH - Neuronal Plasticity/drug effects MH - Phosphorylation/drug effects MH - Prefrontal Cortex/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Rats, Wistar MH - Recognition, Psychology/*drug effects MH - Risperidone/*administration & dosage/blood/*pharmacology MH - Signal Transduction/*drug effects OTO - NOTNLM OT - Antipsychotic OT - Brain volume OT - Cognition OT - Neurotrophin OT - Schizophrenia EDAT- 2020/01/17 06:00 MHDA- 2021/01/08 06:00 CRDT- 2020/01/17 06:00 PHST- 2019/09/18 00:00 [received] PHST- 2020/01/09 00:00 [revised] PHST- 2020/01/12 00:00 [accepted] PHST- 2020/01/17 06:00 [pubmed] PHST- 2021/01/08 06:00 [medline] PHST- 2020/01/17 06:00 [entrez] AID - S0091-3057(19)30470-8 [pii] AID - 10.1016/j.pbb.2020.172853 [doi] PST - ppublish SO - Pharmacol Biochem Behav. 2020 Feb;189:172853. doi: 10.1016/j.pbb.2020.172853. Epub 2020 Jan 13.