A model of increased impulsivity in rats with bilateral parkinsonism treated with Pramipexole

Impulse control disorders (ICD) is a common side effect of the dopaminergic treatment in patients with Parkinson's disease, which is more associated with dopamine agonists than with levodopa. To understand its pathophysiology, reliable animal models are essential. Using the variable delay-to-signal (VDS) paradigm, impulsivity was evaluated in bilateral parkinsonian rats treated with pramipexole (PPX). In this test, rats have to introduce the snout into a nose poke that is signaled by a light (presented at variable delays) triggering the delivery of a food reward after a correct response. Reaching a stable baseline performance, a partial bilateral dopaminergic lesion with 6-OHDA was induced in the dorsolateral striatum (AP: +1mm, L: ±3.4mm, V:-4.7 mm, Bregma). Rats undertook the VDS test under 5 conditions: basal state, 6-OHDA-induced lesion, the effect of two doses of PPX (0,25mg/kg and 3mg/kg; Latin-square design), and the day after the last dose of PPX. Only the acute administration of 3 mg/kg of PPX significantly rised the number of premature responses, indicating an increase of impulsive behavior, in parkinsonian but not in sham rats. Both doses of PPX significantly decreased the accuracy of responding (correct/total number of responses) and increased the incorrect and perseverative (compulsive behavior) responses in both parkinsonian and sham treated groups when compared with saline-treated groups. In conclusion, PPX induced attention deficit (lack of accuracy) as well as compulsive behavior in control and parkinsonian rats, but increased impulsivity only in the parkinsonian animals. This model could constitute a valid tool to investigate the pathophysiology of ICD.

Effects of palmitoylethanolamide in cocaine-induced behaviours

Aims. Cocaine addiction is a chronically relapsing disorder characterized by the compulsion to seek and take the drug. Previous investigations have demonstrated that several drugs of abuse, as cocaine, can alter the levels of lipid-based signalling molecules such as the N-acylethanolamines (NAEs). In addition, NAEs levels in the brain are sensitive to cocaine self-administration and extinction training. In this context, this study aimed to investigate the effect of repeated and acute palmitoylethanolamide (PEA), an endogenous NAE, on the behavioural effects of cocaine using mouse models of conditioned reward and psychomotor activation. Methods. Using male C57BL/6J mice, the ability of repeated PEA injections (1 or 10 mg/kg i.p) to modulate the development of a conditioned place preference (CPP) and behavioural sensitization (BS) induced by cocaine (20 mg/kg i.p.) was evaluated. In addition, the expression of cocaine-induced CPP and BS after acute PEA administration was also studied. Results. PEA (1 and 10 mg/kg i.p) significantly reduced the development of cocaine-induced BS, but did not modify the acquisition of cocaine-induced CPP. Furthermore, both doses of PEA were able to reduce the expression of BS and CPP. Conclusions. Altogether, these findings show that exogenous administration of PEA attenuated psychomotor activation and impaired the expression of CPP induced by cocaine. Our results may be relevant in order to understand the role of NAEs in the development and treatment of cocaine addiction.