The necessity of testing psychoactive drugs in awake freely moving animals has led to the development of a telemetry-based system which enables the pharmacologist to follow centrally active molecules in their time- and dose-dependent effects on electric brain activity in terms of changes in spectral power density of extracellularly recorded field potentials (tele-EEG). This report describes the effect of three analgesics with respect to bioelectric changes in frontal cortex, thalamus, striatum and reticular formation. Two opiate drugs, morphine and tramadol, behaved very similarly despite a tenfold difference in dosage, whereas flupirtine, a nonopiate analgesic, changed the frequency content of the EEG signals in an entirely different manner. The frequency pattern produced by the opiates closely resembles that of centrally acting serotonin uptake inhibitors and thus is consistent with the view of a serotonergic prevalence of neurochemical interactions within the recorded brain areas. In contrast, the action of flupirtine obviously can be attributed to a clonidine-like effect on noradrenergic alpha2-receptors. The results are discussed with respect to already known influences of these drugs on indoleaminergic and catecholaminergic transmission.
Streptozocin-diabetic rats were treated with a mixture of gangliosides (Cronassial, 21% GM1, 40%GD1a, 16% GD1b, 19% GT1b) in different application schemes: a) daily s.c. injection of 20 mg/kg gangliosides starting from the first day of diabetes and continued for 8 weeks; b) application of the same dose but only every second day over the same period of time; c) daily application of the same dose is started four weeks after induction of diabetes and continued for 4 weeks; d) daily injections of a corresponding volume of physiological saline. Serial in vivo determinations of conduction velocities in the tail nerve of these animals and of non-diabetic control animals gave the following results: 1. The nerve conduction velocities decreased in all diabetic groups which is evidence for the development of a peripheral diabetic neuropathy. 2. The finding from a previous study is reproduced showing that daily application of gangliosides counteracts this deceleration of nerve conduction. 3. Application of the same dose every second day is nearly as effective in inhibiting the development of the diabetic neuropathy as daily injections. 4. When a daily ganglioside treatment is started four weeks after the onset of diabetes, the existing neuropathy is reduced. The possible basis for this ganglioside effect on experimental peripheral neuropathy and its significance for the treatment of human diabetic polyneuropathies is discussed.
To establish normal ranges for assessment of autonomic dysfunction, a battery of cardiovascular reflex tests was performed in 120 healthy subjects aged 15–67 years using a computer‐based technique. Tests of heart rate variation (HRV) included 8 measures at rest: coefficient of variation (CV), root mean squared successive difference (RMSSD), spectral analysis of HRV in the low frequency, mid frequency, and high frequency bands in the supine and standing postures; 5 measures during deep breathing: CV b , RMSSD b , Expiration‐Inspiration (E‐I) difference, E/I ratio, and mean circular resultant of vector analysis; Valsalva ratio, and max/min 30:15 ratio. In addition, the change in systolic and diastolic blood pressure in response to standing and the diastolic blood pressure response to sustained handgrip were determined. The results of all measures, the blood pressure tests excepted, declined significantly with increasing age ( r = −0.16 to −0.59; p < 0.05). Moreover, RMSSD, RMSSD b , and E‐I difference decreased considerably with increasing heart rate ( r = −0.37 to −0.52; p < 0.001). The longest and shortest R‐R intervals in response to standing were distributed within beats 21–39 and 6–24, respectively. All tests were independent of sex. Log transformation was used to define the age‐related lower limits of normal at the 2.3 centile for all tests of HRV, except for the E/I, Valsalva, and max/min 30:15 ratios. The results of these tests had to be analysed using a log( y ‐1) transformation. The intra‐individual reproducibility determined on two consecutive days in 20 healthy subjects and 21 diabetic patients indicated that there were no major differences between the two groups regarding the day‐to‐day variation of test results, which was highest for the Valsalva ratio. We conclude that: (1) all indices of spectral and vector analyses of HRV are age‐dependent and have the advantage of being independent of heart rate; (2) RMSSD, E‐I difference, and the 30:15 ratio as it was used previously are not suitable for evaluation of autonomic dysfunction in diabetes; (3) log( y ‐1) transformation is required to determine age‐dependent normal ranges and reproducibility for the three ratios.
Rare side effects on the central nervous system including dizziness, restlessness, and even very rare convulsions as reported during the course of antibiotic treatment with quinolones were the topic of a well-controlled in vitro approach. The excitability of brain matter was tested by electrically evoking field potentials in the CA1 region of the rat hippocampus in vitro. Direct effects of nalidixic acid, enoxacin, pefloxacin, norfloxacin, ofloxacin, and ciprofloxacin were found to occur as a dose-dependent increase in amplitude of this field potential, which is in line with the view that the quinolones increase excitability. The highest increase was found with enoxacin and nalidixic acid, and the lowest increase was found with ciprofloxacin. In order to keep the potential risk of the antibiotic therapy as low as possible, ciprofloxacin might be the drug of choice of the quinolones. In contrast to the quinolones, which only increased the amplitudes of electrically evoked potentials, fenbufen induced spontaneous firing in the pyramidal cell layer without stimulation in addition to its dose-dependent effects on the amplitudes of the evoked potentials. Threshold doses of the quinolones tested (0.25 microM) increased the amplitudes of evoked potentials in the presence of an otherwise ineffective concentration of fenbufen (1 microM) to different degrees, ranging from 39.2% for ciprofloxacin to 72.6% for enoxacin.
Abstract Recording, telemetric trandmission, and spectral analysis of field potentials from frontal cortex, hippocampus, striatum, and reticular formation of the rat brain were used to monitor the effect of tenilsetam (CAS 997) and piracetam on the central nervous in delta and alpha 2 power in all brai areas. Dose‐dependent decreases in alpha 1 power were seen in the frontal cortex, striatum, and reticular formation, whereas the hippocampal alpha 1 activity increased (100 mg/kg) or remained unaffected. These effects were dose‐dependent and lasted for at least 90 min. In the presence of piracetam, changes in brain electrical activity were dominated by an overall decrease in alpha 1 activity and by less pronounced effects on beta 1 activity. The spectral pattern profile induced by tenilsetam was compared to the “fingerprints” of a great number of different drugs from our data base. Some similarities to the action of fluvoxamine and SK&F 38393 point to changes in serotonergic and dopaminergic transmission. The present data show the functional outcome of interactions with different aspects of neurotranmission and suggest that the “nootropic” drug tenilsetam enhances vigilance by shifting the balance of neurotransmission to a status resembling low serotonergic and, at the same time, high dopaminergic activity. These drugs obviously not only improve brain function under pathological conditions but can also affects electrical activity of the intact brain.
