Historical group debriefing after combat exposure.

BACKGROUND: Studies of group debriefing after extreme events have failed to show a significant long-term effect of this technique. However, the heterogeneity of the interventions studied and the length of time between debriefing and its assessment do not allow a proper interpretation of these findings. OBJECTIVE: This study evaluates the immediate effect of debriefing in Israeli soldiers exposed to combat. METHOD: Six small units (N = 39) have undergone historical group debriefing within 72 hours of exposure. State anxiety, self-efficacy, and combat evaluation were measured before and immediately after the sessions. RESULTS: Debriefing was followed by reduction in anxiety, improvement in self-efficacy, and increased homogeneity of the group. CONCLUSION: These effects may be attributable to enhancing group cohesion or to a proper beneficial effect of debriefing.

Reversal of early phenobarbital-induced cholinergic and related behavioral deficits by neuronal grafting.

The present experiment was performed to assess the possible restoration of normal maze behavior, as well as parallel muscarinic receptor binding capabilities, in mice pre- or neonatally exposed to phenobarbital. Mice were exposed to phenobarbital prenatally by feeding the mother phenobarbital (3 gkg milled food) on gestation days 9-18 (PreB mice), or neonatally, by daily injections of 50 mg/kg Na phenobarbital to the pups on days 2-21 (NeoB). At adulthood, PreB and NeoB mice were 61.3% and 65% deficient, respectively, in the hippocampus-related Morris maze behavior, as compared to control. Both groups had a 58% increase in their hippocampal muscarinic receptors maximal binding (Bmax) (p < 0.001); the dissociation constant (Kd) was not affected by the phenobarbital exposure. Treated animals and their respective controls received septal cholinergic embryonic graft into the hippocampus. The viability of the transplants was confirmed by AChE histochemistry. Nine weeks later the grafted mice showed significant improvement in the Morris maze (52% for both PreB and NeoB (p < 0.001)). Their Bmax was also reduced from early phenobarbital exposed animals' levels by 15% for PreB and by 25% for NeoB (p < 0.001). The results suggest that early phenobarbital-induced behavioral deficit and their related biochemical alterations can be partially corrected by the appropriate neural grafting, and thus provide further support to the apparent relationship between the early phenobarbital-induced septohippocampal cholinergic alterations and the hippocampus-related behavioral deficits.

Psychophysiology of the posttraumatic stress disorder: from sulfur fumes to behavioral genetics.

Neurophysiological hypotheses regarding the body-mind relationship in stress disorders have been formulated more than 300 years ago. In 1941 Abraham Kardiner ascribed the name "physioneurosis" to the condition known today as posttraumatic stress disorder (PTSD). Psychophysiological studies of PTSD started with the demonstration of increased responsiveness to external stimuli reminiscent of the traumatic event. Later, abnormal responses to mental imagery were studied, and these studies have resulted in new tools for the assessment and diagnosis of the disorder. Recent studies focus on responses to elementary stimulation, such as the auditory startle reflex, thereby exploring basic CNS routines of habituation and stimulus-discrimination. This article reviews the rapidly expanding literature on the psychophysiology of PTSD. Special emphasis is given to recent studies of the auditory startle and to their implications for the neurobiology of PTSD.

Hippocampal cholinergic alterations and related behavioral deficits after early exposure to ethanol.

The present study was designed to ascertain septohippocampal cholinergic alterations and their related behavioral deficits after early exposure to ethanol. Mouse pups were exposed to ethanol, 3 g/kg by daily subcutaneous injection on postnatal days 2-14. At age 50 days, the ethanol-exposed mice had significant reductions from control levels in eight-arm maze performance. For example, on the fourth testing day, the number of correct entries in the ethanol group was 21% below control levels (P < 0.05) and the number of trials needed to enter all arms was 48% above control (P < 0.001). It took the ethanol-exposed mice twice the time to reach criterion than it did control (P < 0.01). A 33% increase from control level in muscarinic receptor number (Bmax) was found in the treated mice of age 22 days and a 64% increase at age 50 days (P < 0.001). However, no differences between control and treated groups could be detected in the presynaptic component of the cholinergic innervation, choline acetyltransferase activity. The results suggest that early ethanol exposure acts on hippocampal function similarly to phenobarbital, probably via alterations in postsynaptic processes in the septohippocampal cholinergic pathways.

Septohippocampal cholinergic changes after destruction of the A10-septal dopaminergic pathways.

Mice were injected bilaterally into the septum with 6-hydroxydopamine and 6 weeks later the hippocampi were assayed for activity of choline acetyltransferase, muscarinic receptor binding capabilities and for formation of inositol phosphate in response to direct (carbachol) or presynaptically elicited (K+) stimulation of the postsynaptic receptors. Levels of dopamine in the septum were reduced by 70% in the lesioned animals and hippocampal choline acetyltransferase was elevated by the same amount. The Bmax of muscarinic binding was significantly reduced without changes in Kd; nevertheless, carbachol-induced stimulation of formation of inositol phosphate was unaffected. The response to K+ was markedly elevated in the 6-hydroxydopamine-treated animals. Thus, the regulatory effect of A10-septal dopaminergic pathways on the septohippocampal cholinergic innervations is both on the presynaptic and postsynaptic levels.

Alterations in septohippocampal cholinergic innervations and related behaviors after early exposure to heroin and phencyclidine.

Mice were exposed to diacetylmorphine (heroin) or phencyclidine (PCP) prenatally or neonatally. At a later age, they were tested for hippocampus-related behavioral deficits and concomitant alterations in the septohippocampal cholinergic innervations. Actually, this is an application of the previously established phenobarbital neuroteratogenicity model to heroin and PCP. Prenatal exposure was accomplished transplacentally by injecting the mother 10 mg/kg heroin or PCP on gestation days 9-18. Neonatal administrations were applied directly by injections of 10 mg/kg of either drug to the pups between neonatal days 2-21. At the age of 50 days, mice exposed to heroin and PCP prenatally exhibited a 107% and 159% increase in their muscarinic cholinergic receptors Bmax, respectively. Neonatal exposure to heroin or PCP caused an 83% and 76% increase in the receptors respectively. On the behavioral level, both prenatal and neonatal exposure to heroin or PCP reduced performance in the hippocampus related eight-arm maze and Morris mazes. Depending on the drug, the test and the period of drug administration, the reduction ranged between 10% and 75%. The results suggest that heroin and PCP induce alterations in the septohippocampal cholinergic innervations and in related behavioral performance. Further studies are necessary in order to connect the biochemical and behavioral events in causal relationships.

Alterations in hippocampal cholinergic receptors and hippocampal behaviors after early exposure to nicotine.

Mice were exposed to nicotine prenatally by injecting the mother with 1.5 mg/kg nicotine SC twice daily on gestation days 9-18 (PreN mice) or neonatally by daily SC injections of 1.5 mg/kg nicotine on postnatal days 2-21 (NeoN mice). At age 50 days, hippocampal muscarinic receptors Bmax of PreN and NeoN mice were 58% and 79% above control, respectively (p less than 0.01); Kd was unaffected by early nicotine exposure. Eight-arm maze performance of nicotine-exposed animals fell behind control level. Both PreN and NeoN made approximately 10% less correct responses in the first eight trials than controls throughout the test period (p less than 0.01). By the last day of testing, PreN needed 23% and NeoN 31% more trials than controls to enter all arms (p less than 0.001). In addition, PreN needed 35 and NeoN 42% more days than controls to reach criterion (p less than 0.05). Similarly, while 61% of controls reached criterion by day 6 only 17% of PreN and 25% of NeoN reached criterion (p less than 0.01). In the Morris maze, PreN needed from 43-119% more time to reach the platform (p less than 0.001). In the spatial probe test, PreN animals made 35% fewer crosses over the area of the missing platform (p less than 0.001). The study suggests that nicotine administered to the fetus or neonate alters septohippocampal chemistry and induces deficits in hippocampus-related behaviors. The possible reversal of the behavioral changes by manipulating the cholinergic innervations should be the subject of future investigations.

Hippocampal cholinergic alterations and related behavioral deficits after early exposure to phenobarbital.

Mice were exposed to phenobarbital (PhB) prenatally and neonatally. Prenatal exposure was accomplished by feeding the mother PhB (3 g/kg milled food) on gestation days 9-18. Neonatal exposure was accomplished by daily injections of 50 mg/kg sodium PhB directly to the pups on days 2-21. Long-term biochemical alterations in the pre- and postsynaptic septohippocampal system, as well as related behavioral deficits, were assessed in the treated animals. Significant increase in B(max) values for binding of [3H]QNB to muscarinic cholinergic receptors was obtained on both ages 22 and 50 in prenatally (40-90%, respectively, p less than 0.001) and neonatally exposed (58-89%, p less than 0.001) mice whereas Kd remained normal. Similarly, a significant increase of inositol phosphate (IP) formation in response to carbachol was found after both prenatal and neonatal exposure to PhB (p less than 0.05). No alterations in choline acetyltransferase (ChAT) activity were observed in the prenatally or neonatally treated animals. The early exposed mice showed deficits in the performance in Morris water maze, a behavior related to the septohippocampal pathway. The results suggest that early exposure to PhB induces alterations in postsynaptic components of the hippocampal cholinergic system and concomitantly to impairment in hippocampus-related behavior.

Auditory startle reflex in post-traumatic stress disorder patients treated with clonazepam.

Manifestations of acute hyperarousal in the Post-Traumatic Stress Disorder (PTSD) have been assimilated with panic attacks. This study examines the auditory startle reflex in PTSD patients treated with clonazepam, a benzodiazepine with anti-panic properties. PTSD patients treated with clonazepam did not differ from drug-free PTSD patients in the magnitude and the habituation rate of their responses to an auditory startle, with both groups showing abnormally slow habituation. It is suggested that the mechanisms underlying phasic hyperarousal in PTSD might differ from those which have been implied in the genesis of panic attacks.

Neural and behavioral alterations after early exposure to phenobarbital.

Mice who were exposed to phenobarbital prenatally (B mice) had at adulthood deficits in the hippocampal eight-arm maze, spontaneous alternations, and water maze behaviors. Morphological studies revealed neuronal losses in the hippocampus. The surviving neurons had reductions from control in the number of dendritic branches, area and spine density, but wider fission angle than control. Neurochemical studies on the hippocampus revealed the following alterations: (a) decrease in NE level and the number of the NE cell bodies (b) no change in the serotonergic system (c) an increase in muscarinic receptors Bmax in the hippocampus; (d) no changes in GABA and benzodiazepine receptors. However, neonatal phenobarbital exposure caused an increase in the Bmax of GABA and benzodiazepine receptors. Transplantation of fetal septal cholinergic neurons into the hippocampus of B mice reversed most of the deficits in eight-arm maze behavior, while transplantation of noradrenergic cells did not affect the performance of B mice. In further studies on cholinergic mechanisms, the dopaminergic innervations in the septum (originating from A10), which are known to indirectly inhibit the activity of the septohippocampal cholinergic pathways, were destroyed by 6-OHDA. B mice treated with 6-OHDA had an increase in hippocampal ChAT activity and improved their eight-arm maze performance. Thus, understanding of the mechanism of a particular behavioral deficit enables one to correct it despite the nonspecific action of the neuroteratogen.