thiopental and Memory-Disorders

Sedative-hypnotic drugs impair memory, but details regarding the nature of this effect are unknown. The influences of propofol, thiopental, and dexmedetomidine on the performance of a task that isolates specific components of episodic memory function were measured.. Working (1 intervening item, 6 s) and long-term memory (10 intervening items, 33 s) were tested using auditory words in a continuous recognition task before and during drug administration. Eighty-three volunteer participants were randomly assigned to receive a constant target concentration of drug or placebo, producing sedative effects from imperceptible to unresponsiveness. Responsive participants were categorized as high or low performers, using a median split of long-term memory performance during drug administration. Recognition of words at the end of the study day was assessed.. High performers had acquisition of material into long-term memory when drug was present at the same level as placebo. Retention of this material at 225 min was significantly less for propofol (39 +/- 23% loss of material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low performers was evident in multiple measures. Memory for words presented before drug was no different from that associated with placebo for all groups.. Lack of retention of material acquired into long-term memory during propofol administration, associated with minimal sedation, seems to define drug-induced amnesia. Sedation seems to impair the acquisition or encoding of material into long-term memory. Therefore, the putative targets of drug-induced amnesia by propofol are processes associated with retention of material in long-term memory.

Topics: Dexmedetomidine; Electroencephalography; Female; Humans; Male; Memory Disorders; Pain Measurement; Propofol; Reaction Time; Thiopental

The authors prospectively investigated the ability of thiopental to decrease neuropsychiatric complications as a consequence of open-ventricle operations requiring cardiopulmonary bypass. Eighty-nine randomly assigned patients received sufficient thiopental to maintain electroencephalographic silence throughout the period from before atrial cannulation to termination of bypass. These patients received an average of 39.5 mg/kg of thiopental, while 93 control patients received only fentanyl. On the first postoperative day, five thiopental (5.6%) and eight control (8.6%) patients exhibited clinical neuropsychiatric abnormalities. By the tenth postoperative day, all neuropsychiatric dysfunction had resolved in the thiopental group but persisted in seven (7.5%) control patients (P less than 0.025). The incidence of complications was significantly related to calcification of replaced valves, aortic valve replacement, advanced age, and prolonged bypass, but not to low blood pressure during perfusion. The authors believe their data are consistent with embolism as the most important cause of sensory-motor neurologic dysfunction following cardiopulmonary bypass. The data also provide evidence that thiopental in sufficient dosage can reduce the clinical consequences of these events. This is the first demonstration of cerebral protection by a barbiturate in humans.

Topics: Age Factors; Aged; Barbiturates; Blood Pressure; Calcinosis; Cardiopulmonary Bypass; Delusions; Electroencephalography; Female; Hallucinations; Heart Valve Prosthesis; Humans; Male; Memory Disorders; Middle Aged; Myocardial Contraction; Neuropsychological Tests; Postoperative Complications; Sleep Stages; Thiopental; Time Factors

A variety of cardiovascular and cerebrovascular diseases are associated with alterations in cholesterol levels and metabolism. Moreover, convincing evidence shows that high cholesterol diet can lead to learning and memory impairments. On the other hand, a significant body of research has also demonstrated that learning is improved by elevated dietary cholesterol. Despite these conflicting findings, it is clear that cholesterol plays an important role in these cognitive properties. However, it remains unclear how this blood-brain barrier (BBB)-impenetrable molecule affects the brain and under what circumstances it provides either detrimental or beneficial effects to learning and memory. The aim of this study was to characterize the effects of 5% cholesterol diet on six-month-old inbred Brown Norway rats. More important, we sought to examine the role that cholesterol can play when repeated anesthesia and intravenous infusion disrupts cognitive function. This present study supports previous work showing that enriched cholesterol diet leads to significant alterations in neuroinflammation and BBB disruption. Following repeated anesthesia and intravenous infusion of saline we observe that animals under normal diet conditions exhibit significant deficiencies in spatial learning and cholinergic neuron populations compared to animals under enriched cholesterol diet, which do not show such deficiencies. These findings indicate that cholesterol diet can protect against or counteract anesthesia/infusion-induced cognitive deficits. Ultimately, these results suggest that cholesterol homeostasis serves an important functional role in the brain and that altering this homeostasis can either exert positive or negative effects on cognitive properties.

Topics: Animals; Cerebral Cortex; Cholesterol; Cholesterol, Dietary; Choline O-Acetyltransferase; Cognition Disorders; Male; Maze Learning; Memory Disorders; Neurons; Rats; Thiopental

Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R) complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity.. Using an in vitro model of SPW-R activity we found that thiopental (50-200 muM) significantly and concentration-dependently reduced the incidence of SPW-R events (it increased the inter-event period by 70-430 %). At the concentration of 25 muM, which clinically produces mild sedation and explicit memory impairment, thiopental significantly reduced the quantity of ripple oscillation (it reduced the number of ripples and the duration of ripple episodes by 20 +/- 5%, n = 12, P < 0.01), and suppressed the rhythmicity of SPWs by 43 +/- 15% (n = 6, P < 0.05). The drug disrupted the synchrony of SPWs within the CA1 region at 50 muM (by 19 +/- 12%; n = 5, P < 0.05). Similar effects of thiopental were observed at higher concentrations. Thiopental did not affect the frequency of ripple oscillation at any of the concentrations tested (10-200 muM). Furthermore, the drug significantly prolonged single SPWs at concentrations >/=50 muM (it increased the half-width and the duration of SPWs by 35-90 %). Thiopental did not affect evoked excitatory synaptic potentials and its results on SPW-R complexes were also observed under blockade of NMDA receptors. Phenobarbital significantly accelerated SPWs at 50 and 100 muM whereas it reduced their rate at 200 and 400 muM. Furthermore, it significantly prolonged SPWs, reduced their synchrony and reduced the quantity of ripples only at the clinically very high concentration of 400 muM, reported to affect memory.. We hypothesize that thiopental, by interfering with SPW-R activity, through enhancement of the GABAA receptor-mediated transmission, affects memory processes which involve hippocampal circuit activation. The quantity but not the frequency of ripple oscillation was affected by the drug.

Topics: Action Potentials; Anesthetics, Intravenous; Animals; Anticonvulsants; Biological Clocks; Dose-Response Relationship, Drug; GABA-A Receptor Agonists; Hippocampus; Male; Memory; Memory Disorders; Nerve Net; Neural Pathways; Organ Culture Techniques; Phenobarbital; Rats; Rats, Wistar; Receptors, GABA-A; Synaptic Transmission; Thiopental

Topics: Anesthesia, Intravenous; Cerebral Ventricles; Electrocardiography; Electrolytes; Humans; Hyperkalemia; Jugular Veins; Male; Memory Disorders; Middle Aged; Pneumoencephalography; Succinylcholine; Thiopental