Peroxisome proliferator-activated receptor-γ activation attenuates harmaline-induced cognitive impairments in rats.

Cognitive and motor disturbances are serious concerns of the tremors induced by motor disorders. Despite the lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor. Recent studies have shown that PPAR-γ agonists have neuroprotective effects. In the current study, the effects of pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma agonist, on harmaline-induced motor and cognitive impairment were studied. Male Wistar rats were divided into vehicle (normal saline), PIO (20 mg/kg i.p.), harmaline (10 mg/kg, i.p.) and PIO + harmaline (PIO injected 2 h before harmaline) groups. Open field, rotarod, wire grip, foot print and Morris water maze tests were used to evaluate the motor and cognitive performance. The results indicated that administration of PIO attenuated harmaline-induced locomotor, anxiety-like behaviors, and spatial learning and memory impairments, but it partially decreased the tremor score. The neuroprotective and anxiolytic effects of PIO demonstrated in the current study can offer the PPAR-γ receptor agonism as a potential therapeutic agent in the treatment of patients with tremor that manifest mental dysfunction.

Cannabinoid receptor agonism suppresses tremor, cognition disturbances and anxiety-like behaviors in a rat model of essential tremor.

Cognitive and motor disturbances are serious consequences of tremor induced by motor disorders. Despite a lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor. In the current study, the effects of WIN55, 212-2 (WIN), a cannabinoid receptor (CBR) agonist, on harmaline-induced motor and cognitive impairments were studied. Adult rats were treated with WIN (0.5mg/kg; i.p.) 15min before harmaline administration (10mg/kg; ip) after which exploratory and anxiety related behaviors, and cognitive function were assessed using open-field behavior and shuttle box tests. Rats that received harmaline only exhibited a markedly reduced number of central square entries when compared to harmaline vehicle-treated controls, whereas those treated with WIN and harmaline showed a significant increase in central square entries, compared to harmaline only treated. The passive avoidance memory impairments observed in harmaline treated rats, was reversed somewhat by administration of WIN. The neuroprotective and anxiolytic effects of WIN demonstrated in the current study can be offered cannabinoid receptor (CBR) agonism as a potential neuroprotective agent in the treatment of patients with tremor that manifest mental dysfunctions.

Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?

Tremor arises from an involuntary, rhythmic muscle contraction/relaxation cycle and is a common disabling symptom of many motor-related diseases such as Parkinson disease, multiple sclerosis, Huntington disease, and forms of ataxia. In the wake of anecdotal, largely uncontrolled, observations claiming the amelioration of some symptoms among cannabis smokers, and the high density of cannabinoid receptors in the areas responsible for motor function, including basal ganglia and cerebellum, many researchers have pursued the question of whether cannabinoid-based compounds could be used therapeutically to alleviate tremor associated with central nervous system diseases. In this review, we focus on possible effects of cannabinoid-based medicines, in particular on Parkinsonian and multiple sclerosis-related tremors and the common probable molecular mechanisms. While, at present, inconclusive results have been obtained, future investigations should extend preclinical studies with different cannabinoids to controlled clinical trials to determine potential benefits in tremor.

The therapeutic potential of Berberine chloride hydrate against harmaline-induced motor impairments in a rat model of tremor.

Essential tremor (ET) is a progressive neurological disorder with motor and non-motor symptoms. It has conclusively been shown that modulation of glutamate receptors could ameliorate ET. Recent studies have suggested that Berberine (BBR) has an inhibitory effect on glutamate receptors. Therefore, BBR may have therapeutic effects on ET. In this study, male Wistar rats (n=10 in each group) weighing 40-60 g were divided into control, harmaline (30 mg/kg, i.p.) and berberine (10, 20 or 50mg/kg, i.p, 15 min before harmaline injection) groups. Open field, rotarod, wire grip and foot print tests were used to evaluate motor performance. The results indicated that the administration of BBR (10 and 20mg/kg) attenuated harmaline-induced tremor in rats, but the beneficial effects of BBR could not be identified at dose 50mg/kg. In addition, BBR ameliorated gait disturbance in doses of 10 and 20mg/kg. The high dose of BBR not only failed to recover step width but also showed an adverse effect on left and right step length. The results indicate that BBR only in dose of 20mg/kg recovers mobility duration. The current study found a dose-dependent manner for the therapeutic effects of BBR in ET. Our study provides the initial evidence for the effects of BBR on motor function. Since BBR exerts its effects mainly through regulation of neurotransmitter release or blocke of NMDA receptors, thus, it is predicted that BBR ameliorate harmaline effect through blockade of NMDA receptors or glutamate release. This is an important issue for future research to evaluate the possible mechanisms involved.