Improved recognition memory and reduced inflammation following β-caryophyllene treatment in the Wistar-Kyoto rodent model of treatment-resistant depression

Persistent low mood, anxiety and cognitive deficits are common symptoms of depression and highly efficacious treatments that address symptoms including cognitive dysfunction are still required. β-caryophyllene (BCP) is a terpene with anti-inflammatory and pro-cognitive properties; however, its efficacy on cognition in depression remains unclear. This study aimed to investigate acute and chronic BCP treatment effects on cognitive, depressive- and anxiety-like behaviours, and inflammation in male and female Wistar-Kyoto (WKY) rats, a rodent model of treatment-resistant depression. Rats were administered either BCP (50 mg/kg) or vehicle (control). Open field (OFT), social interaction, sucrose preference, novel object recognition (NOR) and elevated plus maze (EPM) tests were conducted after acute (1 h) and chronic (2 weeks) treatment. Peripheral plasma inflammatory cytokine levels were examined. BCP acutely increased locomotor activity in the OFT but did not improve social interaction, whereas chronic BCP prevented increased latency to first interaction in females (not males). BCP did not improve sucrose preference or prevent anxiety-like behaviours in the EPM. BCP significantly increased novel object discrimination in the NOR test in male and female WKY rats and reduced cytokine levels after chronic treatment. This study shows for the first time that chronic BCP treatment improved recognition memory and exerted anti-inflammatory properties in a rodent model of depressive-like behaviours. BCP did not significantly improve anxiety-like behaviours, social interaction or anhedonia in WKY rats of either sex. These findings demonstrate the pro-cognitive effects of BCP in a rodent model of treatment-resistant depression worthy of further investigation.