Abstract

Levetiracetam (LEV) is an antiepileptic drug and is used in the management of various types of seizures and other clinical conditions, including anxiety and neuropathic pain. Its unique mechanism primarily involves selective interaction with synaptic vesicle protein 2A (SV2A), which stabilizes synaptic function and the release of neurotransmitters. The objective of the present study was to evaluate LEV activity in morphine (MPH) dependence. In mice, LEV was used at doses ranging from 31.25 to 125 mg/kg, depending on the experimental paradigm. It was studied in three schedules: (1) MPH tolerance to antinociceptive effects (the hot plate test—HPT); (2) MPH withdrawal signs, manifested as jumps, induced by naloxone (NAL)—2 mg/kg, i.p.; (3) MPH sensitization to locomotor activity. In this study, LEV reduced MPH tolerance to analgesic effects. Moreover, LEV diminished the intensity of NAL-precipitated MPH withdrawal signs. This drug was also effective in attenuating MPH-induced sensitization. These findings suggest that LEV may modulate behavioral adaptations associated with repeated MPH exposure. However, further mechanistic studies are required to identify the molecular and neurochemical pathways involved in these effects.

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