2008, volume 24, issue 4

Only for Pharmacotherapy in Psychiatry and Neurology

Learning, memory and drugs of abuse: the progress in knowledge about mechanisms and treatment of addiction?

Wojciech Kostowski
Farmakoterapia w Psychiatrii i Neurologii, 2008, 4, 191–200

Drug addiction is a complex brain disorder characterized by compulsion to seeking and taking drugs despite severe consequences to health and social relationships. One feature of addiction is that it accompanies exposure to drugs having different pharmacological mechanisms. One of the most interesting hypothesis proposed in recent years, is that neuronal processes thought to form the cellular basis for learning (e.g. long-term potentiation, LTP) may occur in the mesolimbic reward system after drug exposure. This review describes briefl y behavioral processes underlying drug addiction (particularly the behavioral sensitization) and examines the processes ( such as glutaminianergic transmission, LTP formation and protein synthesis) underlying memory consolidation and reconsolidation. Theoretically, new fi ndings on memory have implication for treatment of drug addiction. For example, pathological drug-related memories may be disrupted after their acquisition and consolidation by impairing their reconsolidation after retrieval.

Review article

De novo protein synthesis and memory processes in instrumental conditioning: new perspectives in the treatment of psychiatric disorders

Paweł Mierzejewski
Farmakoterapia w Psychiatrii i Neurologii, 2008, 4, 201–210

The paper presents the actual knowledge about possibilities of infl uencing on memory processes in instrumental conditioning by protein synthesis inhibitors (PSIs) and a possibility of therapeutic application of PSIs in the treatment of psychiatric disorders. The author discussed the role of de novo protein synthesis in the brain in the processes of consolidation, retrieval, reconsolidation and extinction of instrumental responding. Moreover the effects of PSIs on memory processes in classical and instrumental conditioning were compared and differences between their effects on these processes discussed.

Review article

The role of dopaminergic system in pathogenesis of depressive disorders

Dominika Dudek, Marcin Siwek
Farmakoterapia w Psychiatrii i Neurologii, 2008, 4, 211–220

The aim of this review was to discuss the role of dopaminergic pathways in pathogenesis and treatment of depressive disorders. The growing body of evidence from experimental and clinical studies suggests that dopamine may play as important role in the patophisiology of depression as serotonine and noradrenaline. Long-lasting administration of andidepressants results in enhancement of dopaminergic transmission and increased activity of postsynaptic D2/D3 receptors, especially in nucleus accumbens and prefrontal cortex. Dopaminergic agents may induce manic switches (e.g. L-DOPA in the treatment of Parkinson disease), have the antidepressant properties (e.g. bupropion) or may augment the effi cacy of standart antidepressants (eg. 1. antiparkinsonic drugs: pramipexole, amantadine, bromocripine, cabergoline; 2. psychostimulants: methylfenidate, amphetamine and derivates); 3. antypical antipsychotics with dopaminergic proerties: aripiprazole, amisulpride). Dopaminergic drugs may be – used in monotherapy or cambined treatment – may be a very important alternative in cases of drug-resistance or subtype of depression with predominance of psychomotor retardation, anhedonia, somnolence, decreased energy and lack of motivation. These symptoms may be a result of disturbed dopaminergic neurotransmission.

Review article

Movement disorders during levodopa treatment among patients with Parkinson’s Disease

Urszula Fiszer
Farmakoterapia w Psychiatrii i Neurologii, 2008, 4, 221–226

Movement disorders constitute a main issue in the Parkinson’s Disease (PD). They may be considered as an expression of the disease, as well as a side effect of the levodopa treatment, which was refl ected in the diagnosis criteria. A clear response to levodopa and occurrence of dyskinesias related to its application are recognized as typical syndromes of this disease. Movement disorders occurring after the levodopa treatment is connected with the central and peripherial mechanisms. Central mechanisms include progression of nigrostratial degeneration, changes in the dopaminergic receptors and levodopa impact. Peripherial mechanisms are related to absorption and levodopa mechanism. The purpose of therapeutical procedure in PD is the reduction of clinical syptoms and undesired effects of the applied pharmacotherapy.

Review article

Amisulprid for Patients with schizophrenia update of evidence 2008

Małgorzata Rzewuska
Farmakoterapia w Psychiatrii i Neurologii, 2008, 4, 227–242

Amisulpride, a benzamide derivative belongs to a second generation of antipsychotics. It is characterized by higher affi nity for dopaminergic receptors D2/D3 in the limbic rather than in the striatal regions. Amisulpride at low doses antagonize presynaptic D2 and D3 receptors, resulting in enhanced dopamine transmission; however at high doses block postsynaptic receptors, resulting in reduced dopamine transmission.
Clinical effectiveness of amisulpride: antipsychotic effects at high dosages (400-800 mg/d) and reducing of negative symptoms at low dosages (50-300 mg/d) is a consequence of preferential affinity for D2/D3 receptors at low doses and blocking of postsynaptic receptors at high doses. Amisulpride has preferential affi nity for limbic and hippocampal structures and low affi nity for striatal structures which may account for its low potential to induce extrapyramidal adverse effects.
Clinical trials with patients in acute phase of schizophrenia revealed that amisulpride was at least as effective in the control of positive symptoms as haloperidol, flupentixol, ziprasidone, olanzapine and risperidone, and more effective than haloperidol in the control of negative symptoms. Amisulpride signifi cantly reduced persistent negative symptoms in long term treated patients. In the long-term treatment, amisulpride appeared to be more effective and better tolerated than haloperidol and similarly effective as risperidone and olanzapina. Quality of life and social functioning were improved signifi cantly more with amisulpride than other antipsychotics.
All clinical trials showed good tolerability profile of amisulpride and its low influence on extrapyramidal system, weight gain and metabolism of glucose and lipids.
Amisulpride is associated with slight weight gain, and does not seem to be associated with diabetogenic effects.
Influence of amisulpride on the prolactine level is dose related.
Amisulpride is an effective and well tolerated first line atypical antipsychotic used in patients with acute schizophrenia as well as in the long-term maintenance therapy.

Review article

Clinical methods of glutamatergic NMDA receptor modulation in treating schizophrenia

Dominik Strzelecki
Farmakoterapia w Psychiatrii i Neurologii, 2008, 4, 243–248

Article describes clinical possibilities of glutamatergic NMDA receptor modulation in schizophrenia. Clinical trials indicate that glycine site agonists of the NMDA receptor (glycine, D-serine, D-cycloserine, D-alanine) or glycine transporter inhibitors (sarcosine) may moderately (ca. 10-20%) reduce negative symptoms when used as adjuvants to antipsychotics but with exception of clozapine. Treatment is well-tolerated, frequency of signifi cant side effect is similar as in placebo groups.