Subthalamic 5-HT(1A) and 5-HT(1B) receptor modulation of RU 24969-induced behavioral profile in rats

The effects of systemic administration of the serotonin (5-HT)(1A/1B) agonist 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)1H-indole (RU 24969) on locomotor and investigatory behavior in rats have been well characterized using the behavioral pattern monitor (BPM). To elucidate the neural circuitry underlying this behavioral profile, intracerebral dose--response studies were conducted at two sites with high densities of 5-HT(1B) receptors, the subthalamic nucleus (STN) and substantia nigra. Infusion of RU 24969 into the STN produced systemic RU 24969-like changes in locomotor activity and patterns but an uncharacteristic increase in investigatory holepokes. Intra-STN administration of the selective 5-HT(1A) receptor agonist 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) produced RU 24969-like changes in locomotor patterns only, while the 5-HT(1B) receptor agonist 3(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one dihydrochloride (CP-93,129) increased locomotor activity, produced no change in locomotor patterns and nonsignificantly increased holepokes. Intranigral infusion of RU 24969 produced systemic and intra-STN RU 24969-like increases in locomotor activity. Intranigral RU 24969, however, failed to produce any changes in locomotor patterns or investigatory holepokes. Intranigral infusions of CP-93,129 or 8-OH-DPAT had no effects on locomotor activity, locomotor patterns or investigatory holepokes. These results provide evidence for multiple-site mediation of the locomotor-activating effects of RU 24969 and for a dissociation of the neural substrates underlying locomotor and investigatory components of the RU 24969-induced behavioral profile.     

Typical but not "atypical" antipsychotic effects on startle gating deficits in prepubertal rats

RATIONALE: Dopamine (DA) agonists and NMDA antagonists disrupt sensorimotor gating in rats, as measured by a loss of prepulse inhibition of the startle reflex. These effects are used in predictive models for antipsychotic efficacy: clinically "typical" and "atypical" antipsychotics restore PPI in adult rats treated with DA agonists such as apomorphine (APO), while clinically "atypical" antipsychotics restore PPI in rats treated with NMDA antagonists such as phencyclidine (PCP). We previously reported that the PPI disruptive effects of both APO and PCP are evident in 16- to 18-day-old rat pups, suggesting that the brain substrates for these effects are functional very early in development. OBJECTIVE: In the present study we assessed the developmental patterns of antipsychotic effects in these measures. METHODS: The PPI-disruptive effects of APO and PCP, and their antagonism by the typical antipsychotic haloperidol, and the atypical antipsychotic quetiapine, were assessed across development in Sprague-Dawley rats. RESULTS: Similar to the pattern seen in adults, both haloperidol and quetiapine opposed APO-induced PPI deficits in 16- to 19-day-old rat pups. However, the "atypical" antipsychotic quetiapine did not oppose PCP-induced PPI deficits in pups or prepubertal (45 day) adolescents, but did oppose these PCP effects in postpubertal rats. CONCLUSIONS: While brain substrates mediating the PPI-disruptive effects of DA agonists and NMDA antagonists are functional early in development, some physiological event associated with puberty is a necessary condition for the "atypical antipsychotic profile" in this predictive model.     

Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects

Prepulse inhibition (PPI) of the startle reflex refers to the ability of a weak prestimulus, the prepulse, to inhibit the response to a closely following strong sensory stimulus, the pulse. PPI is found to be deficient in a number of psychiatric and neurological disorders associated with abnormalities at some level in the limbic and cortico-pallido-striato-thalamic circuitry. We applied whole-brain functional magnetic resonance imaging to elucidate the neural correlates of PPI using airpuff stimuli as both the prepulse and the pulse in groups of (i) healthy subjects and (ii) schizophrenic patients. Cerebral activation during prepulse-plus-pulse stimuli with stimulus-onset asynchronies of 120 ms was contrasted with activation during pulse-alone stimuli. In healthy subjects, PPI was associated with increased activation bilaterally in the striatum extending to hippocampus and thalamus, right inferior frontal gyrus and bilateral inferior parietal lobe/supramarginal gyrus, and with decreased activation in the right cerebellum and left medial occipital lobe. All activated regions showed significantly greater response in healthy subjects than schizophrenic patients, who also showed a trend for lower PPI. The findings demonstrate involvement of the striatum, hippocampus, thalamus, and frontal and parietal cortical regions in PPI. Dysfunctions in any of these regions may underlie observations of reduced PPI in schizophrenia.     

Developmental markers of psychiatric disorders as identified by sensorimotor gating

Prepulse inhibition (PPI) of the acoustic startle reflex is an operational measure of sensorimotor gating that is amenable to cross-species comparisons. Deficits in PPI have been repeatedly reported in patients with schizophrenia or other psychiatric disorders characterized by abnormalities in sensory, cognitive, or motor gating. Because some forms of schizophrenia appear to be attributable to early developmental perturbations, many animal studies have examined the influences of various developmental manipulations on PPI in adulthood. For example, isolation rearing of rats from weaning into adulthood leads to a reorganization of brain circuitry including changes in monoamine systems that modulate PPI. Isolation rearing of rats leads to deficits in PPI that are not evident pre-puberty, are enduring in adulthood, and are developmentally specific, in that isolation of adult rats does not affect PPI. The PPI deficits in isolation-reared rats are reversed by typical or atypical antipsychotic treatments, including raclopride, haloperidol, clozapine, olanzapine, quetiapine, and even the putative antipsychotic M100907. In contrast, other psychoactive drugs, such as chlordiazepoxide, diazepam, prazosin, or amitriptyline, do not normalize PPI in isolation-reared rats. Hence, the isolation-rearing model may help identify novel antipsychotics. Thus, social isolation rearing of rats provides a developmentally specific, non-pharmacological manipulation that leads to deficits in sensorimotor gating that mimic those observed in schizophrenia patients and are responsive to antipsychotic medications.     

Connections between attachment prototypes and relationship patterns

Connections between attachment styles and relationship patterns are studied on 32 female psychotherapy patients. Our study gives first hints to a connection between attachment variables, assessed by the German version of the Adult Attachment Prototype Rating (AAPR) and predominant relationship patterns, assessed by the Core Conflictual Relationship Theme Method (CCRT) developed by Luborsky, if both methods are used independently. Subsamples according to the attachment styles show differences in CCRT variables.     

The relationship patterns questionnaire (RPQ): validation by using a representative sample

In this study the present form of the Relationship Patterns Questionnaire (RePat) will be presented as a successor of the Interpersonal Relationship Patterns Questionnaire (IRQ). Similar to the IRQ the RePat assesses the behavior of relationship concerning both one's own and the anticipated behavior of an important person on the basis of the SASB model and the CCRT method. In contrast to the IRQ, the RePat is much shorter and thus easier to use. The study describes the construction and the psychometric examination of the questionnaire by using a representative study (n = 2007, East = 1015, West = 992). The samples of East and West Germany show structural differences concerning its relationship patterns, which in our opinion are plausible for political and historical reasons. The clinical application and their implications for therapeutic interventions will be demonstrated by a single case using both the patient's and her partner's assessment of their relationship.     

Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer

PURPOSE: This Phase III study was performed to determine whether chemotherapy plus b.i.d. or q.d. radiotherapy (RT) resulted in superior survival for patients with Stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of 相似文献   

Reduced N-acetylaspartate in the temporal cortex of rats reared in isolation.

BACKGROUND: Isolation rearing of rats is a nonpharmacologic, nonlesion manipulation that leads to deficits in prepulse inhibition (PPI) and other behavioral and neurochemical alterations reminiscent of schizophrenia. N-acetylaspartate (NAA) is present in high concentrations in the central nervous system and is found primarily in neurons. N-acetylaspartate is considered to be a marker of both neuronal loss and cellular dysfunction. Magnetic resonance spectroscopy studies have shown reductions of cortical and hippocampal NAA in schizophrenia, and a recent postmortem study has demonstrated a regionally selective temporal cortex deficit. METHODS: The aim of the present study was to determine whether rats reared in isolation exhibit deficits in PPI and reductions in NAA in discrete brain regions, namely the temporal cortex, frontal cortex, hippocampus, and striatum. RESULTS: Compared with socially housed rats, isolation rearing resulted in PPI deficits (p <.05) and reductions in NAA in the temporal cortex (p <.001), with no significant change in the other regions investigated. CONCLUSION: These results suggest a disturbance of neuronal function, reflected by NAA reductions in the temporal cortex in isolation-reared rats, providing further evidence that isolation rearing can mimic aspects of the neuronal pathology of schizophrenia.