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     

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.     

The value of tartrate resistant acid phosphatase (TRAP) immunoreactivity in diagnosis of hairy cell leukemia

Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder characterized by splenomegaly, pancytopenia, and circulating atypical lymphocytes with circumferential cytoplasmic projections. We investigated the specificity and the sensitivity of anti-TRAP antibody immunoreactivity in 57 cases of HCL. We found that there is a statistically highly significant difference between TRAP immunoreactivities of the study and the control groups, and HCL can be diagnosed by TRAP immunoreactivity in bone marrow trephine biopsy materials with a specificity of 98.27 % and a sensitivity of 100%.     

The use of transdermal fentanyl in chronic non-malignant pain

Twelve non-malignant pain patients were followed-up for pain, improvement in the quality of life, satisfaction for pain therapy and side effects for a mean of 95.25 days with the use of transdermal fentanyl (TDF). During this period a mean of 32.04 mg/gr TDF was used. While the score of pain at rest was decreased by 52.6%, mean pain score on movement was decreased by 45.2% (p= 0.002). Quality of sleep improved and impairment of daily living by pain was decreased significantly (p= 0.002). Satisfaction by the pain therapy was 83.3% and the most common side effect was nausea (16.8%). TDF may be a good alternative in the therapy of chronic non-malignant pain if patients were selected carefully.     

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.