RESUMEN
Studies suggest that the endocannabinoid and endovanilloid systems are implicated in the pathophysiology of schizophrenia. The Spontaneously Hypertensive Rats (SHR) strain displays impaired contextual fear conditioning (CFC) attenuated by antipsychotic drugs and worsened by pro-psychotic manipulations. Therefore, SHR strain is used to study emotional processing/associative learning impairments associated with schizophrenia and effects of potential antipsychotic drugs. Here, we evaluated the expression of CB1 and TRPV1 receptors in some brain regions related to the pathophysiology of schizophrenia. We also assessed the effects of drugs that act on the endocannabinoid/endovanilloid systems on the CFC task in SHRs and control animals (Wistar rats - WRs). The following drugs were used: AM404 (anandamide uptake/metabolism inhibitor), WIN55-212,2 (non-selective CB1 agonist), capsaicin (TRPV1 agonist), and capsazepine (TRPV1 antagonist). SHRs displayed increased CB1 expression in prelimbic cortex and cingulate cortex area 1 and in CA3 region of the dorsal hippocampus. Conversely, SHRs exhibited decreases in TRPV1 expression in prelimbic and CA1 region of dorsal hippocampus and increases in the basolateral amygdala. AM404, WIN 55,212-2 and capsaicin attenuated SHRs CFC deficit, although WIN 55,212-2 worsened SHRs CFC deficit in higher doses. WRs and SHRs CFC were modulated by distinct doses, suggesting that these strains display different responsiveness to cannabinoid and vanilloid drugs. Treatment with capsazepine did not modify CFC in either strains. The effects of AM404 on SHRs CFC deficit was not blocked by pretreatment with rimonabant (CB1 antagonist) or capsazepine. These results reinforce the involvement of the endocannabinoid/endovanilloid systems in the SHRs CFC deficit and point to these systems as targets to treat the emotional processing/cognitive symptoms of schizophrenia.
Asunto(s)
Síntomas Afectivos/metabolismo , Moduladores de Receptores de Cannabinoides/metabolismo , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Endocannabinoides/metabolismo , Esquizofrenia/metabolismo , Síntomas Afectivos/inducido químicamente , Animales , Ácidos Araquidónicos/agonistas , Ácidos Araquidónicos/antagonistas & inhibidores , Ácidos Araquidónicos/metabolismo , Ácidos Araquidónicos/farmacología , Ácidos Araquidónicos/uso terapéutico , Agonistas de Receptores de Cannabinoides/farmacología , Agonistas de Receptores de Cannabinoides/uso terapéutico , Disfunción Cognitiva/inducido químicamente , Endocannabinoides/agonistas , Endocannabinoides/antagonistas & inhibidores , Masculino , Alcamidas Poliinsaturadas/agonistas , Alcamidas Poliinsaturadas/antagonistas & inhibidores , Alcamidas Poliinsaturadas/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Esquizofrenia/inducido químicamente , Esquizofrenia/prevención & controlRESUMEN
OBJECTIVE: Neuro-trophins are critically involved in neuro-plasticity, the impairment of which is a major role-player in bipolar disorder (BD), and their altered levels have been recently advocated in the patho-physiology of this affective malady. The aim of this study, therefore, was to evaluate the plasma levels of nerve growth factor (NGF) in BD patients in comparison with control subjects. METHODS: Forty-nine BD type-I individuals (30 in mania and 19 in euthymia) and 36 healthy controls were assessed by Mini-plus, Young mania and Hamilton depression rating scales. NGF levels were detected by ELISA. RESULTS: Plasma NGF concentrations were decreased in BD patients when compared to that seen with controls. BD individuals in mania had lower NGF levels than euthymic patients or controls. NGF levels were negatively correlated with the severity of mania. CONCLUSIONS: This is the first study to evaluate NGF levels in BD patients, providing further support to the hypothesis of impaired neuro-plasticity in BD. These data also suggest that NGF measurement could be used for the biological marker for manic state.