Chronic phencyclidine treatment impairs spatial working memory in rhesus monkeys

Area of Science:

• Neuroscience
• Primatology
• Pharmacology

Background:

• Phencyclidine (PCP) induces schizophrenia-like behaviors and cognitive deficits, making it a valuable tool for creating animal models of schizophrenia.
• PCP primarily affects frontal dopaminergic function, leading to cognitive impairments, particularly in tasks like the spatial delayed response (SDR).

Purpose of the Study:

• To investigate the long-term effects of chronic PCP treatment on SDR performance in rhesus monkeys.
• To determine if incremental PCP dosing increases the severity and duration of SDR deficits.

Main Methods:

• Nonhuman primates underwent constant intramuscular PCP dosing (0.3 mg/kg) for up to eight weeks, with SDR performance monitored.
• Locomotor activity and blood cortisol levels were assessed during PCP treatment.
• A separate incremental dosing procedure was initiated five months later.

Main Results:

• Constant PCP dosing caused hyperactivity and impaired SDR performance, with deficits peaking at specific treatment days.
• SDR performance returned to baseline levels within a week after discontinuing constant dosing.
• Incremental PCP dosing impaired SDR performance initially but recovery occurred within the treatment period.

Conclusions:

• Repeated phencyclidine administration appears to increase the severity of spatial delayed response deficits.
• Incremental dosing protocols did not exacerbate the severity or duration of PCP-induced SDR deficits in this study.