Topiramate evokes pharmacological activity via a blockade of voltage-dependent sodium channels, reduction in glutamate release, inhibition of AMPA receptors and kainate receptors, and potentiation of GABAergic neurotransmission. Therefore, it is used not only as an antiseizure drug but is also effective in migraine prophylaxis, cluster headaches, neuropathic pain, and alcohol dependence. The aim of this study was to investigate the effect of topiramate in morphine dependence in mice, particularly in terms of morphine tolerance, morphine withdrawal signs, and morphine sensitization. In these experiments, topiramate was administered both acutely and chronically. Topiramate significantly reduced the morphine tolerance in the hot-plate test and attenuated naloxone-induced morphine withdrawal signs. Its effect on morphine sensitization to the locomotor activity of mice was poor. The obtained results showed that topiramate might be an effective drug for reducing the physical symptoms of morphine dependence.

Background: Linagliptin, a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor approved for the treatment of type 2 diabetes, enhances glucagon-like peptide-1 (GLP-1) signaling. Because GLP-1 receptors are widely expressed in the brain, DPP-4 inhibitors have emerged as potential modulators of central nervous system function. The present study investigated the effects of linagliptin (10 and 20 mg/kg, i.p.) on ketamine- (10 mg/kg, i.p.) and diazepam-induced (2 mg/kg, i.p.) deficits in passive avoidance performance in mice. Behavioral effects were assessed using the passive avoidance test, and brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex and hippocampus were determined by enzyme-linked immunosorbent assay (ELISA). Linagliptin attenuated ketamine- and diazepam-induced deficits in passive avoidance performance. In addition, both acute and chronic administration of linagliptin increased BDNF levels in the prefrontal cortex but not in the hippocampus. These findings provide preliminary evidence that linagliptin modulates passive avoidance performance in mice and is associated with increased BDNF levels in the prefrontal cortex. Further studies employing complementary behavioral paradigms and additional molecular approaches are required to clarify the neuropharmacological mechanisms underlying these effects.

Levetiracetam, a second-generation antiepileptic drug, is effective in therapy of various types of seizures. Its pharmacological properties are increasingly used in diversified clinical conditions such as anxiety and neuropathic pain. Levetiracetam has unique mechanism of action - it selectively binds to the synaptic vesicle protein 2A (SV2A), which stabilizes synaptic function and reduces neurotransmitter release, distinguishing it from traditional antiepileptics. The aim of the present paper was to investigate whether levetiracetam (31.25; 62.5 mg/kg, ip) may also be effective drug in reducing of symptoms in morphine dependence in mice. It was studied in three paradigms: 1) morphine tolerance to antinociceptive effect measured in the hot plate test; 2) naloxone-induced (2 mg/kg, ip) morphine withdrawal signs (manifested as jumpings); 3) morphine-induced behavioral sensitization to the locomotor activity of mice. Levetiracetam, at least in one of the doses used, was effective drug in reduction of all measured parameters. The study highlights the need for further research on levetiracetam properties, because it seems to be an innovative target in morphine dependence.

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.