143 In the reserpinetreated rat model of PD, the dopamine D2 receptor agonist quinpirole caused a significant alleviation of the akinesia. This effect was significantly reduced by coinjection with the cannabinoid receptor agonist WIN 55,212-2. The simultaneous administration of the CB1 antagonist

rimonabant with quinpirole and WIN 55,212-2 blocked the effect of WIN 55,212-2 on quinpirole-induced alleviation of akinesia.144 In animal experiments, chronic levodopa produced increasingly severe orolingual involuntary Inhibitors,research,lifescience,medical movements which were Neratinib in vivo attenuated by WIN 55,212-2. This effect was also reversed by rimonabant.145 In other studies, rimonabant was found to possess some beneficial effects on motor inhibition typical of PD, at least in some doses. The injection of 0.1 mg/kg of rimonabant partially attenuated the hypokinesia shown by PD animals with no effects in control rats, whereas higher doses (0.5-1.0 mg/kg) were not effective.146 Inhibitors,research,lifescience,medical A nigrostriatal lesion by MPTP is associated with an increase in CB1 receptors Inhibitors,research,lifescience,medical in the basal

ganglia in humans and nonhuman primates; this increase could be reversed by chronic levodopa therapy, which suggests that CB1 receptor blockade might be useful as an adjuvant for the treatment of parkinsonian motor symptoms.147 High endogenous cannabinoid levels are found in the cerebrospinal fluid of untreated PD patients.148 Administration of inhibitors of endocannabinoid degradation reduced parkinsonian

motor deficits in vivo.149 Thus, both agonists and antagonists of CB receptors seem to help in some parkinsonian symptoms. In clinical trials, the cannabinoid receptor agonist nabilone significantly reduced Inhibitors,research,lifescience,medical levodopainduced Inhibitors,research,lifescience,medical dyskinesia in PD.150 THC improved motor control in a patient with musician’s dystonia.151 In contrast to these findings, some studies find no effect of cannabinoids on PD: orally administered cannabis extract resulted in no objective or subjective improvement in either dyskinesias or parkinsonism,152 no significant reduction in dystonia following treatment with nabilone,153 and rimonabant could not improve parkinsonian motor disability154 However, an anonymous questionnaire sent to all patients oxyclozanide attending the Prague Movement Disorder Centre revealed that 25 % of the respondents had taken cannabis and 45.9 % of these described some form of benefit.155 Thus cannabinoids seem to be able to treat at least some symptoms of neurological diseases.156-158 Huntington’s disease (HD) or Huntington’s chorea (“chorea” meaning “dance” in Greek) is a disorder characterized by a distinctive choretic movement, progressive motor disturbances, dementia, and other cognitive deficits. Neuropathologically, HD is characterized by a degeneration of medium spiny striato-efferent γ-aminobutyric acid (GABA)ergic neurons and by an atrophy of the caudate nucleus.