Glucocorticoid mechanisms may contribute to ECT-induced retrograde amnesia.

RATIONALE: Cortisol levels rise sharply immediately after electroconvulsive therapy (ECT); the resultant stimulation of steroid receptors in the hippocampus may be beneficial or harmful to cognition, depending on the magnitude of the stimulation. Steroid mechanisms may therefore modulate ECT-induced amnesia. OBJECTIVES: Using mifepristone (a glucocorticoid receptor antagonist) as a chemical probe, we sought to examine steroid mechanisms in an animal model of ECT-induced retrograde amnesia. MATERIALS AND METHODS: Adult, male Wistar rats (n = 68) trained in a step-through passive-avoidance task were randomized to receive mifepristone (20 or 40 mg kg(-1) day(-1)) or vehicle (control). These treatments were administered 1 day before the electroconvulsive shock (ECS) course and, again, 1 h before each of five once-daily true (30 mC) or sham ECS. Recall of pre-ECS learning was tested 1 day after the last ECS. RESULTS: Relative to sham ECS, true ECS resulted in significant retrograde amnesia in the vehicle group but not in either of the mifepristone groups. In sham ECS-treated animals, mifepristone did not significantly influence recall. In ECS-treated rats, the higher but not the lower dose of mifepristone was associated with significant protection against the retrograde amnesia evident in the vehicle group. CONCLUSION: Mifepristone administered before the ECT seizure may attenuate ECT-induced retrograde amnesia. This suggests that glucocorticoid mechanisms may contribute to ECT-induced retrograde amnesia.

Evaluation of anxiolytic potential of Celastrus oil in rat models of behaviour.

The Celastrus oil, extracted from seeds of Celastrus paniculatus tested at 2 dose levels (1 and 1.5 g/kg), exhibited significant anxiolytic activity and did not produce tolerance. The non-sedative nature and reversal of buspirone induced behaviour (in open field exploration) point to the serotonergic mechanism underlying the anxiolysis, inspiring further research.

Individual and combined effects of N6-cyclopentyladenosine, flunarizine and diazepam on aminophylline-induced recurrent generalized seizures in mice.

Protective effects of anticovulsant agents, N6-cyclopentyladenosine (CPA) and flunarizine (FLN) against aminophylline (AMPH) (280 mg/kg)-induced convulsions were tested in different groups of mice. All drugs were administered by intraperitoneal route. CPA (2 mg/kg and 4 mg/kg) delayed the time to onset of clonic convulsions (p < 0.05). The standard drug diazepam (DZP, 2.5 mg/kg) increased the time to onset of clonic and tonic convulsions to a statistically significant extent (p < 0.05 and p < 0.01, respectively). The AMPH-induced mortality (90.9%) was significantly reduced (p < 0.02) following the test anticonvulsants--CPA (2 mg/kg and 4 mg/kg), FLN (10 mg/kg) and the combination of CPA with FLN (though not to a significant extent), indicating partial involvement of adenosinergic and calcium related mechanisms, while DZP afforded maximum protection. However, none prevented the mortality in mice over 24 h. The results show the lethal effects of AMPH-induced seizures and involvement of multiple and complex neurotransmitter systems in this process which requires further investigation.

Effects of pulse amplitude, pulse frequency, and stimulus duration on seizure threshold: a laboratory investigation.

BACKGROUND: Stimulus intensity during electroconvulsive therapy (ECT) is reckoned in units of charge (mC). The values of pulse amplitude, pulse width, pulse frequency, and stimulus duration can be varied to yield different composite stimuli, all of which have the same charge. There is little information on the extent to which variations in these stimulus parameters influence the seizure threshold at constant charge in the context of ECT. METHODS: We administered once daily electroconvulsive shocks (ECS) to two groups of rats, starting with a stimulus intensity of 1 mC and increasing in 1 mC steps until the thresholds of each of three different types of seizure were identified. In one group (n = 10), the charge was raised first by increasing pulse amplitude and later by increasing pulse frequency. In the other group (n = 10), the charge was raised by increasing the stimulus duration only. RESULTS: The mean seizure threshold ranged from 8.4 to 11.4 mC, depending on the type of seizure described, in the group in which pulse amplitude and frequency were manipulated; this range was 2.5 to 5.5 mC in the group in which the stimulus duration was manipulated (p < 0.001 for each of three types of seizures). Rats (n = 7) that did not convulse with an 8-mC stimulus in the amplitude and frequency group all convulsed with a 5-mC stimulus from the stimulus duration schedule. The first manifestation of seizure activity was significantly less likely to be generalized with amplitude and frequency titration than with stimulus duration titration (20% vs. 90%, respectively). The mean motor seizure durations (at different thresholds) were comparable with the two methods of stimulus titration. CONCLUSIONS: Seizure thresholds are lower when stimulus duration is the parameter that is increased during dose titration. The many clinical implications of this finding require study.