The role of locus coeruleus nucleus TRPV1 receptors in the development and expression of morphine dependence.

OBJECTIVES: This study investigated the role of locus coeruleus (LC) nucleus TRPV1 receptors (TRPV1r) in the expression and development of morphine physical dependence by intra-LC administration of AMG9810 (selective TRPV1r antagonist) in male Wistar rats. MATERIALS AND METHODS: For assessing the development of morphine dependence, AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered before each morphine administration for seven continues days (once daily; 6, 16, 26, 36, 46, 56, and 66 mg/kg; sc). Furthermore, for evaluating the expression of morphine dependence, a single dose of AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered to morphine-dependent rats on day 8 of the experiment. RESULTS: Obtained data demonstrated that co-administration of TRPV1r antagonist with morphine reduced the development of morphine withdrawal syndrome somatic signs induced by naloxone. Moreover, single intra-LC administration of TRPV1r antagonist on the final day of the examination period significantly decreased the expression of some signs of morphine withdrawal in rats. CONCLUSION: The results showed that LC TRPV1r might be participating in the expression and development of morphine dependence.

The effect of orexin-A on motor and cognitive functions in a rat model of Parkinson's disease.

OBJECTIVE:  The aim of this study was to evaluate the effect of orexin-A (OX-A) and the orexin-1 receptor antagonist SB-334867 (SB) on motor and cognitive functions in a rat model of Parkinson's disease. METHODS: Parkinson was induced by intracerebroventricular (i.c.v) injection of 6- hydroxydopamine (6-OHDA) (200 µg/rat). 72 h later, the treatment was initiated by i.c.v administration of SB (30 nmol/rat) and/or OX-A (0.3 nmol/rat) for 10 days. Motor functions were monitored using rotarod and hanging tests. Cognitive function was assessed by passive avoidance test (Shuttle box). Results: OX-A administration in 6-OHDA treated rats remarkably increased the time which animals run on rod (in rotarod test) and also the latency to fall (in hanging test) (P < 0.01 and P < 0.001, respectively). Conversely, administration of SB in 6-OHDA-treated rats decreased the mentioned indices (P < 0.05 for latency to fall). Administration of agonist and/or antagonist of orexin-1 receptors had no significant effect on 6-OHDA induced cognitive impairment in rats. CONCLUSION:  Results of this study suggest that the orexinergic system might be involved in sensory-motor deficits of Parkinson's disease.

The role of transient receptor potential vanilloid type 1 in unimodal and multimodal object recognition task in rats.

BACKGROUND: The role of transient receptor potential vanilloid type 1 (TRPV1) channels in learning and memory processes has recently been recognized. In the present study, the role of this receptor in the multisensory integration process was investigated. METHODS: This study was done using 96 male Wistar rats, which were kept in a reverse 12-12h dark/light cycle. Unimodal and multimodal object recognition task was performed by four variations of the spontaneous object recognition (SOR) test including standard SOR, tactile SOR, visual SOR, and cross-modal visual-tactile SOR (CMOR). AMG9810 (selective TRPV1 antagonist) was injected into the right lateral cerebral ventricle prior to sample and choice phases of SOR. A discrimination ratio was calculated to assess the preference of the animal for the novel object. RESULTS: Results demonstrated that administration of AMG9810 prior to the sample phase, as encoding phase, and prior to the choice phase, as retrieval phase, impaired discrimination between the novel and the familiar objects in all standard SOR, tactile SOR, visual SOR, and CMOR tasks (all p<0.05). CONCLUSION: The results of this study showed that TRPV1 receptors might be implicated in both unimodal and cross-modal encoding of information in rats.

The effect of Zataria multiflora Boiss hydroalcoholic extract and fractions in pentylenetetrazole-induced kindling in mice.

OBJECTIVE: At present, there are many antiepileptic drugs with a wide range of side effects on the human body. It was assumed that Zataria multiflora Boiss (Z. multiflora) with sedative, anti-spasmodic and anti-inflammatory activity may be effective in the treatment of epilepsy. The aim of the present study was to elucidate the effect of Z. multiflora hydroalcoholic extract and its fraction extracts on pentylenetetrazole (PTZ)-induced chemical kindling. MATERIALS AND METHODS: In this experimental study, eight separate groups of male albino mice were used. All groups received 11 separate intraperitoneal injections of PTZ (35 mg/kg) with two-day intervals. 30 min before the injection of PTZ, mice received vehicle, Z. multiflora hydroalcoholic extract (300 and 600 mg/kg), n-hexane, acetone, methanol fraction extracts (150 mg/kg), or diazepam (10 mg/kg). RESULTS: The kindled mice that were pretreated with vehicle showed a gradual increase in their seizure scores up to the end of the study. The hydroalcoholic extract of Z. multiflora (300 and 600 mg/kg) reduced seizure scores significantly. However, n-hexane, acetone and methanol extracts did not affect seizure scores significantly. CONCLUSION: The present findings demonstrate that the hydroalcoholic extract of Z. multiflora did reduce the severity of seizure attacks in PTZ-induced chemical kindling in mice.