Prolonged deficits of associative motor learning in cynomolgus monkeys after long-term administration of phencyclidine

• Published in: Behavioural brain research 2017-07, Vol.331, p.169-176
• Main Authors: Wu, Bing, Zhao, Xu-dong, Zhang, Hui-min, Li, Xuan, Wu, Guang-yan, Yang, Ying-shan, Tian, Chao-yang, Sui, Jian-feng
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Cerebellum; Conditioning, Classical - drug effects; Eye-blink conditioning (EBC); Female; Learning; Macaca fascicularis; Male; Motor Activity - drug effects; Phencyclidine (PCP); Phencyclidine - administration & dosage; Phencyclidine - pharmacology; Receptors, N-Methyl-D-Aspartate - drug effects; Schizophrenia; Schizophrenia - chemically induced; Schizophrenia - physiopathology; Time
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2017.05.035

•The EBC study was carried out on schizophrenic monkeys without any surgery or permanent attachment of equipment to the animals’ skull for the first time.•We found that PCP can induce enduring deficits of associative motor learning in cynomolgus monkeys after long-term administration.•The effect of PCP on cynomolgus monkeys was sustained even after the injection of PCP for 12 months, and it would make the animals’ learning ability decreased. Phencyclidine (PCP) is a potent drug of abuse that induces sustained schizophrenia-like symptoms in humans by blocking neurotransmission at N-methyl-d-aspartate (NMDA)-type glutamate receptors. Alterations in NMDA receptor function have been linked to numerous behavioral deficits and cognitive dysfunction. Classical eye-blink conditioning (EBC), including delay (dEBC) and trace (tEBC) paradigms, provides an effective means to study the neurobiology of associative motor learning in rodents, mammals and primates. To assess whether administration of low-dosage PCP for extended periods has prolonged effect to alter associative motor learning, in this study 19 adult cynomolgus monkeys were administered PCP (0.3mg/kg, intramuscularly) or saline twice a day for 14days. Twelve–fifteen months after PCP or saline injection, monkeys received dEBC, tEBC, or pseudo-paired training for 6 or 12 successive daily sessions, respectively. The results of this study show that percentage of conditioned response (CR) in dEBC increased as a function of training sessions in both PCP-treated and control monkeys and there was no significant CR% difference between the two groups. However, the CR timing in dEBC of PCP-treated monkeys was significantly impaired, as manifested by shorter CR peak latencies than those of the control group. PCP-treated animals showed significantly lower percentage of CR in tEBC compared to controls. PCP-treated animals were also more sensitive to outside stimuli in tEBC because the UR peak latency of PCP-treated group was significantly lower than the control group. These results indicated that cynomolgus monkeys manifested prolonged deficits in associative motor learning after long-term administration of phencyclidine.