The effect of telmisartan, an angiotensin receptor blocker, on alcohol consumption and alcohol-induced dopamine release in the nucleus accumbens.

Alcohol use disorder remains a major health problem. The mesocorticolimbic dopaminergic system, including the nucleus accumbens region and multiple neural circuits, is involved in its complex underlying mechanism. For instance, alcohol intake stimulates the central and peripheral renin-angiotensin system and increases angiotensin II levels, which predominantly affect angiotensin 1 receptors both in the periphery and in the brain. In this study, we aimed to investigate the effects of the intracerebroventricularly-administered angiotensin 1 receptor blocker telmisartan on the alcohol consumption of male Sardinian alcohol-preferring (sP) rats and on the alcohol-induced dopamine levels in the nucleus accumbens region in Wistar rats. Acute intracerebroventricular administration of telmisartan (100 nM) reduced the alcohol intake for 24 hours without affecting food and water consumption in sP rats. Acute intracerebroventricular injection of the opioid receptor antagonist naloxone (75 nM), tested as a reference compound, also reduced the alcohol consumption in sP rats; however, naloxone's effect lasted only for 30 minutes. In microdialysis experiments, telmisartan administered intracerebroventricularly did not change dopamine levels in the nucleus accumbens that had been induced by acute intraperitoneal alcohol administration in Wistar rats. According to these results, further studies are needed to elucidate the role of the renin-angiotensin system on alcohol use disorder pathophysiology.

The Effects of Fentanyl on Testicular Ischemia-Reperfusion Injury.

OBJECTIVE: Testicular torsion is a condition that often occurs as a result of the rotation of the spermatic cord in childhood and adolescence in men, manifests with acute pain and causes infertility in the future even if emergency intervention is performed. The aim of this study is to investigate the protective and preventive effects of fentanyl, a potent analgesic agent frequently used in anaesthesia practice, on testicular ischemia reperfusion injury, which manifests through acute pain. METHODS: A total of 16 adult male Wistar rats, weighing 200-250 g, were used in this study. They were divided into two groups, consisting of eight animals in each group. Torsion was created in all rats by rotating left testicles 720 clockwise on the day of the experiment. 3 mM of fentanyl was applied intraperitoneally 30 minutes before detorsion to the fentanyl group. Following an hour of ischemia, the left testicle was reinstated, and tissues were repaired according to their physiology. Following 24 hours of reperfusion, the animals were euthanised after taking left testes and blood samples. RESULTS: Fentanyl, administered prior to testicular detorsion, significantly suppressed germ cell damage in torsioned tissue, catalase activity and malondialdehyde levels in blood samples taken from the heart. No significant differences were observed in plasma total thiol concentration, histological score, Leydig cell counts, percentage of necrosis and tubule rupture. CONCLUSION: These findings show that fentanyl administered before detortion creates a protective effect by preventing testicular ischemia reperfusion injury leading to infertility in the future.

The effect of oral administration of monosodium glutamate on epileptogenesis in infant rats.

Glutamate is an excitatory neurotransmitter that is widely distributed throughout the brain. An increase in glutamate concentration or sensitivity of glutamate receptors triggers neurodegenerative diseases, epilepsy in particular. Monosodium glutamate is a substance added to foods to enhance flavour. We investigated the effect of monosodium glutamate on epileptogenesis, as well asheight and weight, in rats that were just weaned. Twenty-four male and female 21-day-old Wistar Albino rats were divided into two groups: one with monosodium glutamate added to the drinking water, and a control in which NaCl was added to the drinking water. The electrical stimulation threshold values were determined in animals to which the hippocampal kindling process was applied, and the stimulations at these threshold values were invariably applied to the animals until they were kindled. The electrical stimulation threshold values of the monosodium glutamate group did not statistically change, whereas the number of required stimulations for kindled rats was significantly lower compared with the control group. These results reveal that long-term oral administration of glutamate salts causes an increase in excitability in the central nervous system during ontogenetic development.

Effect of U-92032, T-Type Ca2+ Channel Blocker, on Rats with Genetic Absence Epilepsy.

INTRODUCTION: Absence epilepsy is associated with diffuse spike-and-wave discharges (SWD) on the electroencephalogram (EEG). Recent studies have demonstrated that the primary somatosensory cortex is also implicated in the generation of the SWDs. OBJECTIVE: This study investigated the effects of systemic and local administrations of U-92032 into the brain of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). METHODS: GAERS animals underwent stereotaxic surgery for the placement of EEG recording electrodes and guide cannulas for U-92032 administration into the lateral ventricle (intracerebroventricular [i.c.v.]), upper lips area (S1Ulp) or barrel field area (S1B) of primary somatosensory cortex. Following 7 days of recovery, electrical activity was recorded continuously for 1 h before and 6 h after intraperitoneal (0.25; 1; 5 mg/kg i.p.) or local U-92032 or dimethyl sulfoxide (DMSO) injections. RESULTS: No changes were detected in the cumulative duration, mean duration, and number of SWDs following i.p. U-92032 injections. Local i.c.v. injections of U-92032 caused a significant decrease in the cumulative duration (i.c.v., 50 and 100 nmol/L), mean duration (i.c.v., 50, 100, and 250 nmol/L), and the number (i.c.v., 250 nmol/L) of SWDs compared to DMSO groups. Intra-cortical (S1Ulp and S1B) U-92032 injections caused a significant decrease in all 3 parameters compared to DMSO groups, as well. CONCLUSION: Intra-cortical injection of U-92032 caused almost complete removal of SWDs in GAERS and i.c.v. administration resulted in a significant reduction. However, systemic i.p. administration did not cause a significant change with the applied -doses.

Effects of Injection of Gamma-Aminobutyric Acid Agonists into the Nucleus Accumbens on Naloxone-Induced Morphine Withdrawal.

AIMS: This study was to investigate the effects of local administration of gamma-aminobutyric acid (GABA) agonists into the nucleus accumbens (NAc) on naloxone-induced morphine withdrawal symptoms. METHODS: Bilateral guide cannulas were stereotaxically implanted in the shell or core regions of the NAc of Sprague-Dawley rats. After a recovery period, 3 morphine pellets, each consisting of 75 mg morphine base, were placed subcutaneously on the first and third days of the study with the rats under mild ether anaesthesia. The GABA agonists, baclofen hydrochloride or muscimol hydrobromide, were injected into the NAc, and morphine withdrawal was induced by naloxone on the fifth day. RESULTS: Administration of baclofen to the shell or core regions of the NAc of Sprague-Dawley rats led to statistically significant decreases in both behavioural and locomotor activity parameters during the morphine withdrawal period, compared to the control group. However, there were no statistically significant changes in locomotor activity or withdrawal behavioural parameters, with the exception of wet dog shakes, between control and muscimol-treated groups. CONCLUSION: These findings show that GABAergic conduction in the NAc is effective on the morphine withdrawal symptoms, and that both the shell and core regions of the NAc are associated with this effect.