Effects of SR141716A on Cognitive and Depression-Related Behavior in an Animal Model of Premotor Parkinson's Disease

Abstract

A previous study from our laboratory revealed that moderate nigral dopaminergic degeneration caused emotional and cognitive deficits in rats, paralleling early signs of Parkinson's disease. Recent evidence suggests that the blockade of cannabinoid CB1 receptors might be beneficial to alleviate motor inhibition typical of Parkinson's disease. Here, we investigated whether antagonism of CB1 receptors would improve emotional and cognitive deficits in a rat model of premotor Parkinson's disease. Depression-like behavior and cognition were assessed with the forced swim test and the social recognition test, respectively. Confirming our previous study, rats injected with 6-hydroxydopamine in striatum presented emotional and cognitive alterations which were improved by acute injection of SR141716A. HPLC analysis of monoamine levels demonstrated alterations in the striatum and prefrontal cortex after SR141716A injection. These findings suggest a role for CB1 receptors in the early symptoms caused by degeneration of dopaminergic neurons in the striatum, as observed in Parkinson's disease.

Behavioral effects of bidirectional modulators of brain monoamines reserpine and d-amphetamine in zebrafish

“…2C for droopy tail phenotypes universally seen in reserpine-treated fish in this study). Finally, it is also possible that both mechanisms contribute to the observed zebrafish and rodent phenotypes in reserpine tests, representing an interesting ‘comorbidity’ (depression/PD) model, as has recently been suggested for other species (Skalisz et al 2002; Tadaiesky et al 2010). …”

Endocannabinoid system in neurodegenerative disorders

“…Rats with 6‐OHDA injected into the striatum exhibit emotional and cognitive alterations that were rescued by acute injection of SR141716A (Tadaiesky et al . ). Blockade of CB1R was shown to protect nigrostriatal dopaminergic neurons against MPTP neurotoxicity by inhibiting microglial activation (Chung et al .…”

“…Acute injections of L-DOPA or rimonabant produced similar improvements in contralateral forepaw stepping in rats with unilateral 6-OHDA lesions, and their co-administration enhanced stepping more than either drug alone (Kelsey et al 2009). Rats with 6-OHDA injected into the striatum exhibit emotional and cognitive alterations that were rescued by acute injection of SR141716A (Tadaiesky et al 2010). Blockade of CB1R was shown to protect nigrostriatal dopaminergic neurons against MPTP neurotoxicity by inhibiting microglial activation (Chung et al 2011).…”

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