ABSTRACT
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.
Subject(s)
Affective Symptoms/metabolism , Cannabinoid Receptor Modulators/metabolism , Cognitive Dysfunction/metabolism , Disease Models, Animal , Endocannabinoids/metabolism , Schizophrenia/metabolism , Affective Symptoms/chemically induced , Animals , Arachidonic Acids/agonists , Arachidonic Acids/antagonists & inhibitors , Arachidonic Acids/metabolism , Arachidonic Acids/pharmacology , Arachidonic Acids/therapeutic use , Cannabinoid Receptor Agonists/pharmacology , Cannabinoid Receptor Agonists/therapeutic use , Cognitive Dysfunction/chemically induced , Endocannabinoids/agonists , Endocannabinoids/antagonists & inhibitors , Male , Polyunsaturated Alkamides/agonists , Polyunsaturated Alkamides/antagonists & inhibitors , Polyunsaturated Alkamides/metabolism , Rats , Rats, Inbred SHR , Rats, Wistar , Schizophrenia/chemically induced , Schizophrenia/prevention & controlABSTRACT
Endocannabinoid system has attracted the researchers to investigate into its ever fascinating roles governing many of the physiological functions in the human body. The prime endogenous cannabinoids are arachidonoylethanolamide also called anandamide and 2-arachidonoylglycerol. Recent pharmacological advances point out that this system of molecules are in initial stages and by updating our current knowledge, we could innovatively design molecules for suitable interventions that could be potentially beneficial to the mankind.
