Central adenosinergic system and its clinical importance

Adenosine is a neuromodulator widely distributed throughout thebody. Since it is continuously synthesized, it can be concluded thatthere is a basal adenosinergic tonus, which has inhibitory effects ingeneral. All of the three adenosine receptors are G-protein coupled.While A1and A3receptor subtypes inhibit adenylate cyclase, A2subtypes activates it. A1and A2Areceptor subtypes, which bindadenosine with high affinity, are responsible for the basaladenosinergic tonus in physiological conditions. The most widelydistributed subtype, A1, is concentrated particularly in cerebral cortex,cerebellum and hippocampus. Adenosine has intense interactionswith other receptor systems. There are antagonistic interactionsbetween A1 dopamine D1and between A2and D2receptors.Adenosine is implicated in physiological processes such as initiationand maintenance of sleep, modulation of arousal, and control ofcerebral blood flow in response to energy demand of the brain.Adenosine is also implicated in cell-protection in pathologicalconditions like hypoxia and ischemia. Adenosine might be importantin the pathophysiology of anxiety, epilepsy, depression,schizophrenia, Parkinson’s disease, and addiction. The currentliterature about the central adenosinergic system is reviewe

Impact of baseline prepulse inhibition on nicotine-induced locomotor sensitization in rats

The rats having high locomotor reactivity to a novel environment (LRNE) are known to be more vulnerable to develop locomotor sensitization, which reflects the initial neuroplastic changes in brain systems related to addictive behaviours. The present study aimed to investigate whether sensorimotor gating level, measured by prepulse inhibition (PPI) of acoustic startle reflex, also reflects vulnerability for nicotine sensitization. A batch of rats was assigned into three groups according to their baseline PPI values. The highest 1/3 and the lowest 1/3 proportions were selected and defined as high-inhibitory (HI) and low-inhibitory (LI) groups. LRNE was measured in the rats, then they were treated with nicotine (1 mg/kg, tartrate salt, subcutaneously) or saline and locomotor activity (LMA) was immediately recorded for 15 min. This procedure was performed daily for 5 successive days. After a 3-day drug-free period, all rats were challenged with nicotine (1 mg/kg) on 9th day and with saline on 12th day. Same sensitization protocol was applied in another batch of rats, except assigning them into the high-responder (HR) and low-responder(LR) groups according to LRNE levels. There was no significant difference between HI and LI rats in LRNE. Although the acute effect of nicotine on LMA was higher in HI rats, a locomotor sensitization developed and expressed only in LI rats. In the following experiments, nicotine stimulated LMA both in HR and LR rats, but induced and expressed locomotor sensitization only in HR rats. The present study shows that acute locomotor stimulant effect and locomotor sensitization developing effects of nicotine are associated with the baseline PPI and LRNE levels. But these two factors are independent from each other

Mirtazapine does not affect pentylenetetrazole- and maximal electroconvulsive shock-induced seizures in mice

Mirtazapine is an antidepressant exhibiting both noradrenergic and serotonergic activity. We have investigated the effects of mirtazapine on pentylenetetrazole (PTZ)- and maximal electroconvulsive shock (MES)-induced seizures in mice. Mirtazapine (1.25-20 mg/kg) or saline was administered, and locomotor activity was evaluated for 30 min. One hour after administration of mirtazapine (1.25-5 mg/kg) or saline, PTZ (80 mg/kg) was injected intraperitoneally into the mice. Immediately afterward, times of onset of the first myoclonic jerk (FMJ), generalized clonic seizures (GCS), and tonic extension (TE) were recorded. In the MES groups, we used the MES protocol to induce convulsions characterized by tonic hindlimb extension. Similarly, I h after mirtazapine or saline administration, an electroshock was evoked by ear-clip electrodes to induce convulsion. Mirtazapine, at 10 and 20 mg/kg, depressed locomotor activity. Doses of 1.255 mg/kg had no significant effect on the time of onset of FNIJ, GCS, or TE induced by PTZ; on the duration of GCS and TE1- or on the latency to reinstatement of the righting reflex after MES administration. Our results suggest that mirtazapine neither aggravates nor alleviates PTZ- or MES-induced seizures in mice. (c) 2007 Elsevier Inc. All rights reserved.Mirtazapine is an antidepressant exhibiting both noradrenergic and serotonergic activity. We have investigated the effects of mirtazapineon pentylenetetrazole (PTZ)- and maximal electroconvulsive shock (MES)-induced seizures in mice. Mirtazapine (1.25–20 mg/kg) orsaline was administered, and locomotor activity was evaluated for 30 min. One hour after administration of mirtazapine (1.25–5 mg/kg)or saline, PTZ (80 mg/kg) was injected intraperitoneally into the mice. Immediately afterward, times of onset of the first myoclonic jerk(FMJ), generalized clonic seizures (GCS), and tonic extension (TE) were recorded. In the MES groups, we used the MES protocol toinduce convulsions characterized by tonic hindlimb extension. Similarly, 1 h after mirtazapine or saline administration, an electroshockwas evoked by ear-clip electrodes to induce convulsion. Mirtazapine, at 10 and 20 mg/kg, depressed locomotor activity. Doses of 1.25–5 mg/kg had no significant effect on the time of onset of FMJ, GCS, or TE induced by PTZ; on the duration of GCS and TE; or on thelatency to reinstatement of the righting reflex after MES administration. Our results suggest that mirtazapine neither aggravates nor alleviatesPTZ- or MES-induced seizures in mice. 2007 Elsevier Inc. All rights reserved

Effects of pioglitazone and retinoic acid in a rotenone model of parkinson's disease

Parkinson's disease (PD) is a late-onset, progressive and neurodegenerative disorder of unknown etiology. Besides the other therapeutic approaches, new drug options in pharmacotherapy of PD are important. The aim of the present study was to investigate the effects of pioglitazone and retinoic acid, antioxidant and neuroprotective agents, on rotenone-induced model of PD in rats. Adult male Wistar rats (260-373 g) were subjects. Rotenone (2.5 mg/kg, sc) was injected to rats for 70 days. At the end of rotenone administration, rats were treated with pioglitazone (10 mg/kg, ip) and retinoic acid (1 mg/kg, ip) or vehicles for 15 days. Then, rats were tested for evaluation of Parkinson signs by measurement of locomotor activity. In addition, dopamine levels were detected in striatum, hippocampus and hypothalamus in individual groups of control, rotenone and pioglitazone or retinoic acid-treated rats. Rotenone significantly reduced locomotor activity of the rats. It also significantly reduced dopamine levels in striatum and hippocampus, but not hypothalamus. Pioglitazone and retinoic acid reversed in reduction of locomotor activity significantly. Pioglitazone, but not retinoic acid, significantly reversed the reduced striatal dopamine level. Both drugs were ineffective on reduced levels of dopamine in hippocampus. Our results suggest that pioglitazone and retinoic acid have some beneficial effects on rotenone-induced model of PD in rats. Pioglitazone seems to be more effective than retinoic acid. These agents may be helpful for preventing or controlling of some signs of PD.Scientific Research Committee of Gulhane Military Medical Academy (GATA) (AR-2008/25