Abstract—Morphine is known to induce a long-term hyperlocomotor response due to increased dopamine release in the nucleus accumbens via the activation of dopaminergic neurons in the ventral tegmental area. It has been demonstrated that the low-affinity antagonist of NMDA receptors hemantane can alleviate ethanol-induced stimulation of behavior due to its effect on the dopamine- and noradrenergic systems. In the present study, we studied the effects of the aminoadamantane derivative hemantane on the changes in the balance of monoamines and their metabolites in brain structures of C57Bl/6 mice after acute morphine administration. Single i.p. administration of hemantane at a dose of 20 mg/kg did not affect spontaneous locomotor activity per se but alleviated behavior stimulated by s.c. morphine injection at a dose of 20 mg/kg (p < 0.05). In the ex vivo experiments, hemantane prevented a morphine-induced significant increase in the DOPAC/DA and 5‑HIAA/5-HT ratios in the striatum (both p < 0.05) and HVA/DA in the nucleus accumbens (p < 0.01) and promoted the recovery of the DOPAC/DA ratio to the control level in the hypothalamus. These data demonstrate the capability of hemantane to inhibit morphine-induced behavioral stimulation, probably via modulation of the dopaminergic and serotonergic systems.
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Ethical approval. All experiments with animals were performed in accordance with the protocol approved by the Biomedical Ethical Commission of the Zakusov Research Institute of Pharmacology.
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Kolik, L.G., Nadorova, A.V., Narkevich, V.B. et al. Hemantane a Derivative of Aminoadamantane Alleviates Morphine-Induced Hyperlocomotion via Modulation of Activity of the Dopaminergic and Serotonergic Systems. Neurochem. J. 14, 55–63 (2020). https://doi.org/10.1134/S1819712420010134
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DOI: https://doi.org/10.1134/S1819712420010134