In a between-subject comparison of two memantine administration schedules we observed that treatment with the NMDA receptor antagonist memantine before testing sessions reduced ingestion of a 10% sucrose solution in rats, due to reduced licking burst size, thus suggesting a blunted hedonic response. Conversely, daily post-session administration reduced burst number, indicating a reduced level of behavioural activation, likely due to the development of conditioned taste aversion (CTA). In this study, the effect of pre-session and post-session memantine administration was investigated within-subjects. Memantine was administered in daily intraperitoneal injections for 13 days, on alternate days, either 1-h before–“before testing” sessions—or immediately after a 30-min session–“after testing” sessions. The effects on the microstructure of licking for a 10% sucrose solution were examined in the course of treatment and for 21 days after treatment discontinuation. The results show reduced burst size in the “before testing” sessions, without effects on the intra-burst lick rate, an index of motoric effects. Moreover, burst number was reduced since the third session of both administration conditions until the end of treatment. Interestingly, the effect of memantine of reducing the activation of ingestive behaviour was less pronounced in this study with respect to that observed with the previous study post-session administration schedule, in spite of the longer treatment. This apparent paradox might be explained if one considers these effects as instances of a memory-related effect, such as the development of CTA. In the framework of this hypothesis, the “before testing” sessions, not being followed by memantine administration, can be considered as extinction sessions performed every other day. Moreover, the animals treated with memantine at the highest dose failed to recover to pre-treatment ingestion levels 21 days after treatment discontinuation, while the animals treated after testing sessions in the previously published study showed a complete recovery well before the 15^th day test. Within the same interpretative framework, this might depend by the reduced number and frequency of the extinction trials—i.e. the number of the sessions run after treatment discontinuation—in the present study. These results provide further support to the conclusion that memantine administration before sessions reduce burst size, an effect which is likely due to blockade of NMDA receptors occurring during behavioural testing. The observation that this effect can be obtained even in absence of a reduced intra-burst lick rate, which rules out the involvement of motor impairment, provides an important piece of evidence in support to the interpretation of this effect as a blunted hedonic response. Moreover, these results provide further evidence that burst number reduction is due to a memory-related effect induced by memantine administration after sessions.

• Activation
• Anhedonia
• Conditioned taste aversion
• Licking microstructure
• Memantine

This study aimed to evaluate the efficacy of memantine in the acute treatment of geriatric with bipolar disorder (BD) hospitalized for mania.

This study conducted on 70 patients older than 60 years with BD in the acute phase of mania. Oral sodium valproate was prescribed in both groups. The intervention group received memantine tablet and the placebo group received a placebo tablet based on a same procedure. Severity of mania, cognitive changes, and quality of life (QoL) were assessed and recorded 4 and 8 weeks after the beginning of the study. The collected data were analyzed with SPSS (version 20) using independent samples t-test, analysis of variance in repeated observations, Chi-squared test, and Fisher's exact test.

Mania severity score had no significant difference at the beginning of the study, but 4 and 8 weeks after the intervention, it was reduced significantly in both groups (P < 0.001) that was higher in memantine group (P = 0.038). The mean increase in score of cognitive variations was 6.74 in the memantine group and 3.62 in the placebo group with a nonsignificant difference (P = 0.125). The scores of each dimension of QoL in the two groups showed that in all four dimensions, the patient's physical, psychological, social, and environmental status increased significantly by time (P < 0.001).

According to the results of this study, memantine as an adjuvant to administration of sodium valproate may have a significant effect on decreasing the intensity of mania in the long run.

• Bipolar disorder
• geriatrics
• mania
• memantine

Background: Mania seems to be associated with an increased dopamine (DA) transmission. Antidepressant treatments can induce mania in humans and potentiated DA transmission in animals, by sensitizing DA D2 receptors in the mesolimbic system. We have suggested that the sensitization of D2 receptors may be responsible of antidepressant-induced mania. This review aims to report the experimental evidence that led to the hypothesis that antidepressant-induced DA receptors dysregulation can be considered an animal model of bipolar disorder.

Methods: We reviewed papers reporting preclinical and clinical studies on the role of DA in the mechanism of action of antidepressant treatments and in the patho-physiology of mood disorders.

Results: A number of preclinical and clinical evidence suggests that mania could be associated with an increased DA activity, while a reduced function of this neurotransmission might underlie depression. Chronic treatment with imipramine induces a sensitization of DA D2 receptors in the mesolimbic system, followed, after drug discontinuation, by a reduced sensitivity associated with an increased immobility time in forced swimming test of depression (FST). Blockade of glutamate NMDA receptors by memantine administration prevents the imipramine effect on DA receptors sensitivity and on the FST.

Conclusion: We suggest that chronic treatment with antidepressants induces a behavioural syndrome that mimics mania (the sensitization of DA receptors), followed by depression (desensitization of DA receptors and increased immobility time in the FST), i.e. an animal model of bipolar disorder. Moreover the observation that memantine prevents the “bipolar-like” behavior, suggests that the drug may have an antimanic and mood stabilizing effect. Preliminary clinical observations support this hypothesis.

• Animal models
• bipolar disorder
• depression
• mania
• memantine
• mood stabilizer

• Bipolar disorder
• Depression
• Manic symptoms
• Memantine
• Mood stabilizer