Behavioral effects of nicotine, amphetamine and cocaine under a fixed-interval schedule of food reinforcement in rats chronically exposed to caffeine

 Epidemiological surveys demonstrate that caffeine, the main psychoactive ingredient of coffee, is a positive correlate in drug abuse. To characterize the behavioral nature of caffeine interactions with other psychomotor stimulants, we examined the effects of chronic caffeine exposure on the behavioral responses to nicotine, amphetamine, cocaine, the selective D₁ agonist SKF-82958 and the selective D₂ receptor agonist NPA, in rats responding under a fixed interval (FI) schedule of food reinforcement. Following stabilization of rates and temporal patterns of responding (mathematically expressed as quarter-life values, QL), twenty-one Sprague-Dawley rats responding under a 5-min FI schedule of food reinforcement were divided into two groups; one (twelve rats) maintained on tap water (control) and the other (nine rats) on caffeine (3 mg/ml added to the drinking water). Following the substitution of caffeine solution for tap water, behavior was temporarily disrupted as evidenced by decreases in responding and QL values which reached a maximum after 72 h (rate 60% and QL 30% below baseline levels). Rats developed complete tolerance to these effects of caffeine over 5 days of caffeine exposure. After response rate and QL values stabilized, effects of drugs were evaluated. Nicotine (0.01–1.0 mg/kg; SC), amphetamine (0.1–5.6; IP), and cocaine (1.0–17; IP) each produced biphasic dose-dependent changes in response rate with maximum increases in response rate following intermediate doses and decreases in response rates following higher doses. The increase in rates of responding produced by amphetamine or cocaine (but not nicotine) were greater (P<0.05) in caffeine-drinking than in water-drinking rats. Both SKF-82958 (0.001–0.3 mg/kg; IP) and NPA (0.0001–0.1; IP) produced only dose-dependent decreases in rates of responding. Caffeine-drinking rats were less sensitive to the rate-depressant effects of SKF-82958 (P<0.05) than water-drinking rats. However, similar changes (P>0.05) were produced by NPA in both groups. Except for amphetamine, the remaining drugs produced similar (P>0.05) dose-dependent decreases in QL values in water- and caffeine-drinking rats. Amphetamine produced smaller decreases in QL values in caffeine-drinking rats than in water-drinking rats (P<0.05). Chronic exposure to caffeine produced complete insurmountable tolerance to the response-rate increasing (stimulant) effects of acute caffeine (3.0–17 mg/kg; IP) in caffeine-drinking rats. In conclusion, our study revealed that chronic caffeine exposure potentiates the behavioral response to amphetamine and cocaine but not to that of nicotine in rats responding under a FI schedule of food reinforcement. Thus, it is likely that these effects are mediated through different pharmacological mechanisms. Received: 3 September 1997 / Final version: 9 May 1998     

Prophylactic acetylcysteine usage for prevention of contrast nephropathy after coronary angiography

Radiographic contrast agents can cause acute decrease in renal functions. It is thought that anti-oxidant acetylcysteine can prevent contrast nephropathy. Fifty patients planned to undergo elective diagnostic coronary angiography with serum creatinine values above 1.3 mg/dL were included in the study. Acetylcysteine was given orally at a dose of 600 mg twice daily, on the day before and on the day of administration of contrast agent in the acetylcysteine group (n=25). Acetylcysteine was not given to the control group (n=25). Saline (0.9%) was given intravenously at a rate of 1 mL/kg/h for 12 hours before and 12 hours after administration of contrast agent. Contrast nephropathy was detected in 3 of 25 patients (12%) in the acetylcysteine group and 2 of 25 patients (8%) in the control group (P>0.05). Contrast nephropathy was developed in 2 of 4 patients (50%) with baseline serum creatinine concentrations above 2.5 mg/dL, whereas it was developed in only 3 of 46 patients (6.5%) with baseline serum creatinine concentrations below 2.5 mg/dL (P=0.04). It was detected that in patients planned to undergo elective diagnostic coronary angiography with renal dysfunction, oral acetylcysteine and hydration before the procedure was not more effective than hydration alone in the prevention of contrast nephropathy. High baseline serum creatinine values were detected as a risk factor for development of contrast nephropathy.     

Does antioxidant supplementation alter the effects of acute exercise on erythrocyte aggregation, deformability and endothelium adhesion in untrained rats?

This study aimed to determine whether high-dose antioxidant supplementation had an impact on the acute exercise effects related to erythrocyte membrane mechanics. Experimental animals (n=32) were divided into four groups as control, exercised, supplemented, and supplemented + exercise. Four-week antioxidant supplementation (vitamin C, vitamin E, and zinc) was applied to experimental animals. Following acute exercise on a motor-driven rodent treadmill, erythrocyte aggregation and deformability, erythrocyte adhesion to endothelial cells, superoxide dismutase (SOD), and glutathione peroxidase activities of the erythrocytes were analyzed. In both supplemented and non-supplemented exercised groups, there was a significant decrease in SOD activities and erythrocyte aggregation, and an increase in adhesion to endothelial cell although there was no change on erythrocyte deformability. There were no differences in the responses to the exercise of supplemented and nonsupplemented rats. The data suggested that high-dose antioxidant supplementation did not alter the effects of acute exercise on erythrocyte membrane mechanics.     

Effect of amrinone on mucosal permeability in experimental intestinal ischaemia/reperfusion injury

BACKGROUND: The preventive effect of amrinone on ischaemia/reperfusion (I/R) injury has been shown in the medical literature. The purpose of the present study was to investigate the preventive effect of amrinone on I/R injury of the small bowel of the rat. METHODS: Thirty-two Wistar albino rats (140-180 g) were divided into four groups (n = 8). In all groups except the sham group the superior mesenteric artery was clamped for 30 min. At the beginning of reperfusion, 1 mL of 2405 Bq/mL 51Cr-ethylenediamine tetra-acetic acid (EDTA) was administered into the prepared ileal segment. Following 30 min of reperfusion, 1 mL of blood was obtained from the portal vein. After the rats were killed, the small intestine was removed for histopathological studies. A total of 5 mg/kg amrinone was administered to the rats in group 1 before ischaemia and in group 2 before reperfusion, whereas only saline was administered to the rats in the control group. Statistical analysis was carried out with Kruskal-Wallis and chi2 test, P < 0.01 was considered significant. RESULTS: Both the blood 51Cr-EDTA measurements (mean +/- SD) and mucosal injury grades (MIG) were highest in the control group (3.95 +/- 0.71 c.p.m.; MIG, 3-5) followed by group 2 (0.50 +/- 0.35 c.p.m.; MIG, 1-3), group 1 (0.47 +/- 0.34 c.p.m. MIG, 0-3), and sham group (0.12 +/- 0.05 c.p.m.; MIG, 0). The difference between groups 1 and 2 and the control group were statistically significant (P < 0.01 for each comparison). The results of group 1 and 2 were similar statistically (P > 0.05). CONCLUSIONS: Amrinone was found to be effective in preventing intestinal I/R injury.     

Obsessive-compulsive symptoms in schizophrenia: prevalance and clinical correlates

Obsessive-compulsive symptoms (OCS) have been observed in a substantial proportion of schizophrenic patients. In this study, the rate of occurrence of OCS and obsessive-compulsive disorder (OCD) in schizophrenic patients, and also the interrelationship between OCS and schizophrenic symptoms and depressive symptoms were assessed. A total of 100 subjects with a diagnosis of schizophrenia from the 4th edition of the Diagnostic and Statistical Manual (DSM-IV) were evaluated by the structured and clinical interview for axis-1 DSM-IV disorders-patient edition (SCID-P), the Positive and Negative Syndrome Scale (PANSS), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the Calgary Depression Rating Scale for Schizophrenia. The prevalance of OCS in individuals meeting criteria for schizophrenia was 64%. A total of 30 of these patients (Y-BOCS total score > or =7) also met the DSM-IV criteria for OCD. The total score on Y-BOCS was significantly correlated with total score on PANSS, Positive-PANSS score, General-PANSS score and total score on Calgary Depression Rating Scale for Schizophrenia. OCS and OCD relatively frequent in schizophrenic patients and OCS are significantly correlated with the severity of psychosis, positive symptoms, and depressive symptoms in schizophrenic patients. These findings provide further evidence for the importance of OCS in schizophrenia.     

Synaptic plasticity in the central nucleus of the amygdala

In recent years, the amygdala has emerged as a critical site of plasticity for the acquisition of various forms of Pavlovian learning, either aversive or appetitive. In most of these models, the critical site of plasticity has been localized to the basolateral complex of the amygdala (BLA). In contrast, the central nucleus of the amygdala has emerged as a passive relay of potentiated BLA outputs toward downstream effectors. At odds with this view, however, recent studies suggest that the central nucleus may also be a site of plasticity and play an active role in some forms of Pavlovian learning. The present review summarizes the evidence supporting this possibility.