Objective. Hydroalcoholic extract of leaves of Mallotus oppositifolius (MOE), a plant used for CNS conditions in Ghana, was investigated for acute antidepressant effects in the forced swimming (FST) and tail suspension tests (TST). Results. In both FST and TST, MOE (10, 30, and 100？mg？kg？1) significantly decreased immobility periods and frequencies. A 3-day pretreatment with 200？mg？kg？1, i.p., para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor, reversed the decline in immobility and the increase of swimming score induced by MOE in the modified FST. Pretreatment with reserpine alone (1？mg？kg？1), α-methyldopa alone (400？mg？kg？1, i.p.), or a combination of both drugs failed to reverse the decline in immobility or the increase in swimming score caused by the extract in the modified FST. The extract potentiated the frequency of head twitch responses induced by 5-hydroxytryptamine. Pretreatment with D-serine (600？mg？kg？1, i.p.), glycine/NMDA agonist, abolished the behavioural effects of MOE while D-cycloserine (2.5？mg？kg？1, i.p.), a glycine/NMDA partial agonist, potentiated it in both TST and modified FST. Conclusion. The extract exhibited antidepressant effects in mice which is mediated by enhancement of serotoninergic neurotransmission and inhibition of glycine/NMDA receptor activation. 1. Introduction Depression is an extremely common pathological complex with psychological, neuroendocrine, and pathological symptoms [1]. It is a leading cause of disability worldwide and has a very significant impact on morbidity, mortality, and health care cost [2–4]. Disconcertion in monoaminergic neurotransmission especially serotonin and noradrenaline neurotransmission is considered the major cause of the observed symptoms of depression. Unfortunately the efficacy of these medications is unsatisfactory and multiple side effects are common [5]. It is estimated that about 40% of patients have conditions refractory to current medications. Furthermore, these drugs require at least 2–4 weeks of administration before producing clinically meaningful improvement in the symptoms [6]. These reasons underpin the need for novel therapeutic agents with less side effects and faster onset of action [7, 8]. Also both preclinical and clinical studies support the role of NMDA receptor antagonists as possible therapeutic agents for depression [5, 9, 10]. For instance ketamine and memantine have demonstrated rapid and profound antidepressant effects clinically [11, 12]. Numerous behavioural studies have further demonstrated that antagonists and partial agonists at the
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