Antidepressant-induced Dopamine Receptor Dysregulation: A Valid Animal Model of Manic-Depressive Illness.

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.

Failure of memantine to "reverse" quinpirole-induced hypomotility.

Aim: To evaluate antidepressant-like effect of memantine in a rat model.

Methods: Male Wistar rats were treated intraperitoneally with either vehicle, memantine (10 mg/kg) or imipramine (20 mg/kg), for 3 wk. Twenty-four hour after the last treatment animals were challenged with quinpirole (0.

Memantine prevents "bipolar-like" behavior induced by chronic treatment with imipramine in rats.

A great deal of evidence suggests that virtually all antidepressant treatments induce a dopaminergic behavioral supersensitivity. We have suggested that this effect may play a key role not only in the antidepressant effect of these treatments, but also in their ability to induce a switch from depression to mania. In 2003-4 we found that the sensitization of dopamine receptors induced by imipramine is followed, after imipramine withdrawal, by a desensitization of these receptors associated with a depressive-like behavior assessed in the forced swimming test.

Three-year, naturalistic, mirror-image assessment of adding memantine to the treatment of 30 treatment-resistant patients with bipolar disorder.

Background: Developing safe and effective long-term treatments for bipolar disorder remains a major challenge. Given available treatments, patients with bipolar disorder remain unwell in half of long-term follow-up, mostly in depression. As memantine, an N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist used to treat dementia, has been proposed for testing in bipolar disorder, we carried out a 3 + 3-year, mirror-image, chart-review study of the effects of adding memantine to stably continued, but insufficiently effective, ongoing mood-stabilizing treatments.

Memantine: New prospective in bipolar disorder treatment.

Unlabelled: We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer's dementia, is an effective treatment for acute mania and for the prevention of manic/hypomanic and depressive recurrences of manic-depressive illness. Lithium remains the first line for the treatment and prophylaxis of bipolar disorders, but currently available treatment alternatives for lithium resistant patients are of limited and/or questionable efficacy. Thus, research and development of more effective mood stabilizer drugs is a leading challenge for modern psychopharmacology.

Memantine in the treatment and prophylaxis of bipolar type II mood disorder and co-morbid eating disorder: a case report.

We have recently reported that memantine has a clinically relevant antimanic and long-lasting mood-stabilizing effect in treatment- resistant bipolar disorders, both as augmenting agent and as a monotherapy. Moreover, we observed an acute antimanic and sustained mood-stabilizing effect also in "naïve" bipolar type I disorder. Here we report a case history of a young woman suffering from bipolar type II mood disorder, associated with a very severe eating disorder, showing an acute antimanic and a long-term prophylactic effect of memantine on bipolar disorder and comorbid eating disorder.

Memantine in the treatment and prophylaxis of bipolar II disorder and comorbid fibromyalgia: a case report.

We have recently reported that memantine has a clinically relevant antimanic and long-lasting mood-stabilizing effect in treatment-resistant bipolar disorders, both as augmenting agent and as monotherapy. We have also observed an acute antimanic and sustained mood-stabilizing effect in a small number of patients with bipolar I disorder who had had minimal previous pharmacotherapy. In this article, we report the case of a young woman suffering from bipolar II disorder with associated fibromyalgia, in whom memantine showed an acute antimanic and a long-term prophylactic effect on both bipolar disorder as well as the associated fibromyalgia syndrome.

The role of memantine in the treatment of psychiatric disorders other than the dementias: a review of current preclinical and clinical evidence.

Memantine, a non-competitive NMDA receptor antagonist approved for Alzheimer's disease with a good safety profile, is increasingly being studied in a variety of non-dementia psychiatric disorders. We aimed to critically review relevant literature on the use of the drug in such disorders. We performed a PubMed search of the effects of memantine in animal models of psychiatric disorders and its effects in human studies of specific psychiatric disorders.

The sustained mood-stabilizing effect of memantine in the management of treatment resistant bipolar disorders: findings from a 12-month naturalistic trial.

Background: We have recently provided preliminary clinical observations indicating that memantine, as augmenting agent, was associated with a meaningful antimanic and mood-stabilizing effect in treatment-resistant bipolar disorders. To further investigate the therapeutic and prophylactic action of the drug we administered memantine, as augmenting agent, to 40 treatment-resistant bipolar disorder patients, monitored and evaluated for 12 months.

Methods: The sample population encompassed 40 treatment-resistant bipolar disorder patients monitored for 12 months.

Clozapine increases reward evaluation but not overall ingestive behaviour in rats licking for sucrose.

Rationale: Clozapine and the "atypical" antipsychotics are less prone than neuroleptics to induce extrapyramidal motor effects, worsening of the negative symptoms of schizophrenia and dysphoria. This is paralleled by preclinical evidence showing reduced suppression of behaviours aimed at the pursuit of reward, with increased measures of reward efficacy. Serotonin 5-HT2 receptors seem to play a role in determining this profile.

Dopamine on D2-like receptors is involved in reward evaluation in water-deprived rats licking for NaCl and water.

The analysis of licking microstructure provides measures, size and number of licking bouts, which might reveal, respectively, reward evaluation and behavioural activation. Based on the ability of the dopamine D2-like receptor antagonist raclopride to reduce bout size and to induce an "extinction mimicry effect" on bout number, we suggested that the level of activation of reward-associated responses is updated, or "reboosted", on the basis of a dopamine D2-like receptor-mediated evaluation process occurring during the consummatory transaction with the reward. Here we investigate the effects of the dopamine D2-like receptor antagonist raclopride (0, 25, 125, and 250microg/kg) on the microstructure of licking for water and sodium chloride solutions (0.

Dopamine is involved in the antidepressant-like effect of allopregnanolone in the forced swimming test in female rats.

Evidence from both animal and human studies suggests a role for dopamine in the therapeutic effect of antidepressant drugs. Consistently, dopamine receptor antagonists antagonize the effect of antidepressant drugs in different experimental models of depression. Neurosteroids, and in particular allopregnanolone, seem to be involved both in the pathophysiology of depression and in the mechanism of action of antidepressant drugs, and their role seems to be particularly important in the understanding of mood disturbances related to the different phases of the reproductive life in women.

A possible role for the endocannabinoid system in the neurobiology of depression.

The present review synthetically describes the currently advanced hypotheses for a neurobiological basis of depression, ranging from the classical monoaminergic to the more recent neurotrophic hypothesis. Moreover, the Authors review the available preclinical and clinical evidence suggesting a possible role for the endocannabinoid system in the physiopathology of depression. Indeed, in spite of the reporting of conflicting results, the pharmacological enhancement of endocannabinoid activity at the CB1 cannabinoid receptor level appears to exert an antidepressant-like effect in some animal models of depression.

Chronic valproate fails to prevent imipramine-induced behavioural sensitization to the dopamine D2-like receptor agonist quinpirole.

Based on experimental evidence suggesting a relationship between dopamine and mania, we proposed the antidepressant-induced dopaminergic supersensitivity as a model of antidepressant-related mania. We have previously shown the ability of carbamazepine, but not lithium, to prevent this phenomenon. Here we show that sodium valproate (50 mg/kg/day for 3 weeks) fails to prevent imipramine (20 mg/kg/day for 3 weeks)-induced sensitization to the locomotor response to the dopamine D2-like receptor agonist quinpirole (0.

Dopamine D3 receptor antisense oligodeoxynucleotide potentiates imipramine-induced dopaminergic behavioural supersensitivity.

Chronic antidepressant treatments result in the potentiation of dopaminergic transmission in the mesolimbic dopamine system revealed as an increased motor response to dopamine D2-like agonists. On the basis of the involvement of this system in the control of motivation and reward-related behaviour, which are impaired in depression, it has been suggested that such supersensitivity might play an important role in the mechanism of action of these drugs. Several studies have provided evidence suggesting a role of dopamine D3 receptors in mediating antidepressant-induced increased motor response to dopamine agonists.

Long-term imipramine withdrawal induces a depressive-like behaviour in the forced swimming test.

Chronic antidepressant treatments enhance dopaminergic neurotransmission in the mesolimbic dopamine system. We suggested that this potentiation might underlie both the antidepressant therapeutic effect and the antidepressant-induced switch from depression to mania. In a recent study we have shown a reversal of the imipramine-induced dopaminergic supersensitivity after 40 days of chronic imipramine withdrawal.

Dopamine D1 receptor agonists induce penile erections in rats.

The dopamine receptor agonist apomorphine has been recently introduced in the treatment of erectile dysfunction. While it is well established that dopamine D2-like receptors play a crucial role in this effect, conflicting result are reported in the literature as for the role of dopamine D1-like receptors. The aim of this study was to determine the effect of systemic administration of dopamine D1-like receptor agonists on penile erection in rats.

(-)-Linalool produces antinociception in two experimental models of pain.

Linalool is a monoterpene compound commonly found as a major component of the essential oils of several aromatic plant species, many of which are used in traditional medical systems as analgesic and anti-inflammatory remedies. We previously reported that (-)-linalool, the natural occurring enantiomer, plays a major role in the anti-inflammatory activity displayed by different essential oils, suggesting that linalool-producing species are potentially anti-inflammatory agents. In this study, the antinociceptive activity of (-)-linalool was examined in two different pain models in mice: the acetic acid-induced writhing response, a model of inflammatory pain, and the hot plate test, a model of supraspinal analgesia.

Reversal of antidepressant-induced dopaminergic behavioural supersensitivity after long-term chronic imipramine withdrawal.

Chronic antidepressant treatments enhance dopaminergic neurotransmission in the mesolimbic dopamine system. We suggested that this potentiation might underlie both the antidepressant therapeutic effect and the antidepressant-induced switch from depression to mania, which in turn, might be involved in the development of rapid cycling in bipolar patients. In this study, we investigated the changes occurring in the sensitivity of the mesolimbic dopamine system up to 40 days after antidepressant withdrawal.

Synthesis and D(2)-like binding affinity of new derivatives of N-(1-ethyl-2-pyrrolidinylmethyl)-4,5-dihydro-1H-benzo[g]indole-3-carboxamide and related 4H-[1]benzothiopyrano[4,3-b]pyrrole and 5,6-dihydro-4H-benzo[6,7]cyclohepta[b]pyrrole-3-carboxamide analogues.

Various new derivatives and structural analogues of N-(1-ethyl-2-pyrrolidinylmethyl)-4,5-dihydro-1H-benzo[g]indole-3-carboxamide (2a), a representative term of a series of 2-aminomethylpyrrolidinyl derived 4,5-dihydrobenzo[g]indolcarboxamides with good D(2)-like affinity, were synthesized and evaluated for their ability to bind to dopamine D(2)-like receptors in vitro. The structural contribution to D(2)-like receptor binding of the 4,5-dihydrobenzo[g]indole portion of the molecule was examined. From these studies, compound 2k, 2-chloro-N-(1-ethyl-2-pyrrolidinylmethyl)-5,6-dihydro-4H-benzo[6,7]cyclohepta[b]pyrrole-3-carboxamide, was found to possess a potent affinity for D(2)-like receptors.

Different sensitivity to the motor-stimulating effect of amphetamine in Sardinian alcohol-preferring and non-preferring rats.

The selective breeding of rodents on the basis of ethanol intake and preference has led to the development of lines of alcohol-preferring and non-preferring animals. The divergent degree of alcohol preference and consumption displayed by these lines of animals appears to be related, among other factors, to the genetic differences in dopaminergic neurotransmission. Moreover, in genetically unselected rats, a positive correlation has been found between alcohol preference and several amphetamine effects, including the stimulation of motor hyperactivity, thus suggesting the hypothesis that a common neural pathway might underlie some aspects in both of the amphetamine-induced hypermotility and alcohol preference.