Behavioural Responses to Limonene Pretreatment and Morphine in Mice: Hot-Plate, Open-Field, Rotarod, and Forced-Swim Assessments

Abstract

Morphine affects nociceptive responses and motor behaviour in rodents, complicating interpretation of drug interactions. Limonene, a citrus-derived monoterpene, has been reported to exhibit biological activities, but its effects when administered before morphine remain uncertain. Thermal response latency, open-field locomotion, rotarod performance and forced-swim immobility were compared across eight groups of Swiss albino mice receiving saline, limonene, morphine (1, 3 or 5 mg/kg), or limonene before the corresponding morphine dose. The 48 mice (24 females and 24 males; six per group) underwent four assays separated by 15-day intervals. At later nominal hot-plate observation times, several morphine-only groups showed longer latencies than their corresponding combination groups. Morphine-only groups displayed higher open-field square-crossing counts than vehicle at 30–120 min, whereas combination groups generally showed lower counts than morphine alone. Rotarod residence time and forced-swim immobility differed across treatments without a uniform dose-dependent pattern. Findings are descriptive because individual-animal observations, defined statistical contrasts and complete test outputs are not reported. Unresolved dose, timing and recording discrepancies prevent conclusions regarding analgesic enhancement, motor protection, opioid sparing or antidepressant efficacy.