Effects of fluoxetine and PCPA on isolation-induced morphine self-administration and startle reactivity.

The present study investigated the effects of the SSRI fluoxetine and the serotonin synthesis blocker--parachlorophenylalanine (PCPA) on morphine self-administration and startle reactivity in rats subjected to social isolation during adulthood. Adult Wistar rats were housed individually or in pairs for 21days. They were treated with fluoxetine, PCPA, or vehicle and tested for their startle response and intake of a morphine solution (0.5mg/ml). Socially restricted rats consumed significantly more morphine solution (but not water) than rats living in pairs, in both one-bottle and in two-bottle tests. They also showed significantly higher startle response amplitude. Daily fluoxetine treatment (5mg/kg i.p.) counteracted these behavioral alterations induced by isolation housing while PCPA treatment (200mg/kg for 3 consecutive days) further exacerbated it. Social isolation may increase morphine self-administration and emotional reactivity in the startle box by affecting serotonin. Antidepressants (such as fluoxetine) may normalize or stabilize serotonin function and restore the behavioral changes produced by isolation.

Impaired "affective theory of mind" is associated with right ventromedial prefrontal damage.

OBJECTIVE: To examine the hypothesis that patients with ventromedial (VM) frontal lesions are impaired in the affective rather than cognitive facets of theory of mind (ToM). BACKGROUND: Prefrontal brain damage may result in impaired social behavior, especially when the damage involves the orbitofrontal/VM prefrontal cortex (PFC). It has been previously suggested that deficits in ToM may account for such aberrant behavior. However, inconsistent results have been reported, and different regions within the frontal cortex have been associated with ToM impairment. METHOD: The performance of 26 patients with localized lesions in the PFC was compared with responses of 13 patients with posterior lesions and 13 normal control subjects. Three ToM tasks differing in the level of emotional processing involved were used: second-order false belief task, understanding ironic utterances, and identifying social faux pas. RESULTS AND CONCLUSIONS: The results indicated that patients with VM (but not dorsolateral) prefrontal lesions were significantly impaired in irony and faux pas but not in second-order false belief as compared with patients with posterior lesions and normal control subjects. Lesions in the right VM area were associated with the most severe ToM deficit. These results are discussed in terms of the cognitive and affective facets of "mind-reading" processes mediated by the VM cortex.

Impairment in cognitive and affective empathy in patients with brain lesions: anatomical and cognitive correlates.

The present study was designed to examine the degree of impairment in cognitive and affective empathy among patients with focal brain lesions, and the contribution of specific cognitive abilities (such as cognitive flexibility and processing of emotional information), to empathy. The cognitive and affective empathic response of patients with localized prefrontal lesions (n=36) was compared to responses of patients with parietal lesions (n=15) and healthy control subjects (n=19). Results indicate that patients with prefrontal lesions (especially those with lesions involving the orbitoprefrontal and medial regions) were significantly impaired in both cognitive and affective empathy as compared to parietal patients and healthy controls. When the damage was restricted to the prefrontal cortex, either left- or right-hemisphere lesions resulted in impaired empathy. However, when the lesion involved the right hemisphere, patients with parietal lesions were also impaired. The pattern of relationships between cognitive performance and empathy suggested dissociation between the cognitive correlates of affective and cognitive empathy.

Characterization of empathy deficits following prefrontal brain damage: the role of the right ventromedial prefrontal cortex.

Impaired empathic response has been described in patients following brain injury, suggesting that empathy may be a fundamental aspect of the social behavior disturbed by brain damage. However, the neuroanatomical basis of impaired empathy has not been studied in detail. The empathic response of patients with localized lesions in the prefrontal cortex (n = 25) was compared to responses of patients with posterior (n = 17) and healthy control subjects (n = 19). To examine the cognitive processes that underlie the empathic ability, the relationships between empathy scores and the performance on tasks that assess processes of cognitive flexibility, affect recognition, and theory of mind (TOM) were also examined. Patients with prefrontal lesions, particularly when their damage included the ventromedial prefrontal cortex, were significantly impaired in empathy as compared to patients with posterior lesions and healthy controls. However, among patients with posterior lesions, those with damage to the right hemisphere were impaired, whereas those with left posterior lesions displayed empathy levels similar to healthy controls. Seven of nine patients with the most profound empathy deficit had a right ventromedial lesion. A differential pattern regarding the relationships between empathy and cognitive performance was also found: Whereas among patients with dorsolateral prefrontal damage empathy was related to cognitive flexibility but not to TOM and affect recognition, empathy scores in patients with ventromedial lesions were related to TOM but not to cognitive flexibility. Our findings suggest that prefrontal structures play an important part in a network mediating the empathic response and specifically that the right ventromedial cortex has a unique role in integrating cognition and affect to produce the empathic response.

Cooperative social coordination and aggression: II. Effects of sex and housing among three strains of intact laboratory rats differing in aggressiveness.

Pairs of laboratory rats were rewarded with sugar solution for cooperating by means of synchronized shuttling in a rectangular chamber. Learning and performance were compared in males and females of three strains--S3, Charles River, and Wistar--ordered in terms of decreasing levels of aggressiveness. In addition, same-sex pairs of each strain were housed either together or individually. When housed together, males and females of all strains eventually cooperated at comparable levels, with rates of acquisition across strains inversely related to their aggressiveness. Individual housing, in contrast, was associated with severe deficits in males of the S3 and CR strains linked to violent fighting and prolonged freezing by animals who had previously been defeated. All other individually housed groups, including males of the Wistar strain and females of all strains, were able to cooperate, including S3 females whose violent fighting was not associated with immobility by defeated animals. In general, the majority of groups were able to cooperate despite differences in aggressiveness associated with sex, strain, and housing. Possible processes in this accommodation are discussed.

The application of jackknife statistics to estimates of the recombination fraction.

We develop and evaluate the jackknife statistics [Efron, 1982] for obtaining confidence intervals for the recombination fraction. We consider two cases: (1) a single sibship of size S with phase known parents (one doubly heterozygous and one doubly homozygous) and (2) a sample of 20 nuclear families. We compare the jackknife confidence interval to the -1.00 lod and -0.83 lod intervals. For the first case we compare our intervals with a confidence interval which we develop that has coverage of exactly 95%. For the second case, we do a simulation study and compare the coverage of the intervals and the endpoints of the intervals with the actual 2.5th and 97.5th percentiles. Our results indicate that in case (1) the lod intervals provide closer estimates to the 95% exact interval than does the jackknife approach. However, in case (2), although the lod intervals have better coverage probabilities, the jackknife interval endpoints are closer to the actual percentile points than either of the lod interval endpoints.

Gender differences in using alcohol to cope with depression.

To examine gender differences in alcohol consumption as a function of mood and expectancies, 32 nondepressed and 32 moderately depressed male and female social drinkers were compared during a 15-minute taste-rating session. Results indicated that depressed subjects tended to consume more alcohol than nondepressed subjects and men consumed more alcohol than women. Depressed men drank more and drank more per sip than all other subjects. Three depressed men consumed more than all other subjects. Depression and anxiety decreased over time for all subjects. However, a Sex x Depression x Time interaction showed that only depressed men and nondepressed women were substantially less depressed after drinking. The nondepressed women, compared to the depressed men, consumed less alcohol and reported a greater increase in positive mood. Men expected more global positive effects from drinking than women, suggesting the tension reduction hypothesis (TRH) is mediated by gender-specific expectancies.

New health professions after a decade and a half: delegation, productivity and costs in primary care.

Though knowledge about physician's assistants and nurse practitioners is far from conclusive, these new health practitioners (NHPs) appear to perform a large percentage of primary care services at a high level of quality and productivity. Moreover, the gap between the physician/NHP substitution ratio and the NHP/physician cost ratio seems wide enough to assure cost savings when NHPs are used well.

PIP: Although knowledge about physicians' assistants and nurse practitioners is far from conclusive, review of the literature indicates that these new health practitioners (NHPs) appear to perform a large percentage of primary care services at a high level of productivity in the U.S. Moreover, the gap between the physician/NHP substitution ratio and the NHP/physician cost ratio seems wide enough to assure cost savings when NHPs are used well.

Nerve growth factor: enhanced recovery of feeding after hypothalamic damage.

A single intraventricular injection of nerve growth factor (NGF). given at the time of brain damage, facilitated the course of recovery from the lateral hypothalamic anorexic syndrome in male rats. In the second and third weeks after the trauma, NGF-treated rats ate more food, regained body weight more rapidly, and fed more vigorously in response to intraventricular administration of norepinephrine than untreated controls. After full recovery, rats that had been treated with NGF were resistant to reinstatement of the hypothalamic syndrome by 6-hydroxydopamine. NGF may facilitate behavioral recovery by promoting the development of supersensitivity to norepinephrine and possibly also by stimulating the growth of regenerating noradrenergic neurons in the brain.

Benzodiazepines: anxiety-reducing activity by reduction of serotonin turnover in the brain.

The anxiety-reducing effects of minor tranquilizers in the rat conflict test were mimicked by serotonin antagonists and by p-chlorophenylalanine, an inhibitor of serotonin synthesis; the depressant effects of the minor tranquilizers were mimicked by norepinephrine antagonists. Intraventricular injections of serotonin led to a suppression of behavior, and also antagonized the anxiety-reducing action of benzodiazeprines. Intraventricular injections of norepinephrine led to a release of punished behavior from suppression, and also antagonized the depressant action of benzodiazepines. The anxiety-reducing activity, and the decrease in serotonin turnover induced by benzodiazepines, were maintained over repeated doses, whereas depressant activity, and the decrease induced in norepinephrine turnover, both rapidly underwent tolerance. Tranquilizers may exert their anxiety-reducing effects by a reduction of serotonin activity in a behaviorally suppressive punishment system, and they may exert their depressant effects by a reduction of norepinephrine activity in a behaviorally facilitatory reward system.