Antagonism of neuropeptide YY1 receptors does not inhibit ethanol's effects on cortical EEG and ERPs in Wistar rats

OBJECTIVE: Ethanol and neuropeptide Y (NPY) can have additive neurobehavioral effects. In the present study, the NPY Y1 receptor antagonist BIBP3226 was administered alone or in combination with a moderate dose of ethanol to determine whether it interacted with the neurobehavioral effects of ethanol. METHOD: Male Wistar rats were implanted with cortical recording electrodes and a lateral ventricular cannula. The effects of 1 nmol BIBP3226, 0.75 g/kg ethanol and the combination (BIBP3226 + EtOH) on neurophysiological activity and locomotion were then assessed. RESULTS: Ethanol significantly increased 1-2 Hz parietal cortical power and this effect was partially antagonized by BIBP3226. Peak frequencies in the parietal cortical 6-8 Hz and 8-16 Hz bands were also altered by ethanol, but these effects were not reversed by BIBP3226. BIBP3226 or ethanol, when administered alone, did not alter motor activity or cortical event-related potentials (ERPs) but administration of BIBP3226 + EtOH reduced motor activity, reduced parietal cortical N1 ERP amplitude and increased frontal cortical N1 ERP latency. CONCLUSIONS: In the present study, the most prominent effect of antagonizing central NPY Y1 receptors was a facilitation of the effects of ethanol. In particular, the effects of combined administration of BIBP3226 and ethanol are indicative of enhanced sedation and possibly cognitive impairment.     

Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence: relation to anxiety-like and depressive-like behavior

OBJECTIVE: Recently, animal models have been developed that demonstrate that adolescent nicotine exposure produces neurobehavioral changes which persist into adulthood. This study further examined the impact of adolescent nicotine exposure on anxiety-like and depressive-like behavior, as well as on levels of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) in this model. METHODS: Male adolescent rats (35-40 days old) were administered nicotine using Nicoderm CQ patches (Smith-Kline Beecham). Behavior in the elevated plus maze (EPM) and forced swim test (FST) was assessed 2-3 weeks after exposure ended. Brain levels of CRF and NPY were then assessed 5-6 weeks after behavioral tests were completed. In addition, blood and brain levels of nicotine resulting from nicotine treatment were examined. RESULTS: After 5 days of exposure to 5 mg/kg/day nicotine, blood levels of nicotine averaged 66+/-5 ng/ml and brain nicotine levels averaged 52+/-4 ng/g. Rats exposed to nicotine displayed an anxiety-like profile in the EPM (i.e., decreased time spent in the open arms) and an antidepressant-like profile in the FST (i.e., less time spent immobile). Rats exposed to nicotine also had increased hypothalamic and frontal cortical CRF, increased hypothalamic and hippocampal NPY, and a decreased ratio of NPY to CRF in the amygdala. CONCLUSIONS: This study demonstrates that adolescent nicotine exposure produces lasting increases in anxiety-like behavior and may reduce depressive-like behavior. These behavioral changes also occurred in concert with alterations in CRF and NPY systems. Thus, lasting neurobehavioral changes associated with adolescent nicotine exposure may be related to allostatic changes in stress peptide systems.     

Electrophysiological effects of allopregnanolone in rats with a history of ethanol exposure

BACKGROUND: Sensitivity to the anticonvulsant effects of allopregnanolone (ALLO) is enhanced during the early phase of ethanol (EtOH) withdrawal. However, it is unclear whether this enhanced sensitivity generalizes to ALLO's neurobehavioral effects during protracted abstinence. The purpose of this study was to examine the neurophysiological effects of ALLO in rats with a history of chronic EtOH exposure after a protracted period of abstinence. METHODS: Male Wistar rats were exposed to EtOH vapor for 14 hr/day for 5 weeks. Blood EtOH levels were maintained between 200 and 250 mg/dl. The effects of ALLO (0.0-10 mg/kg, intraperitoneally) on motor activity, the electroencephalogram (EEG), and auditory event-related potentials then were assessed after 6 to 8 weeks of abstinence from EtOH. RESULTS: ALLO's effects on the EEG were consistent with previous studies and were unaffected by EtOH exposure. ALLO increased high-frequency EEG power and shifted peak EEG frequencies in a benzodiazepine- and barbiturate-like manner in both the cortex and the hippocampus. The effects of ALLO on event-related potentials were attenuated in rats with a history of EtOH exposure. Low doses of ALLO (1 and 5 mg/kg) reduced cortical P1 amplitude in response to the standard tone but only in the control group. ALLO also increased N1 amplitude in the hippocampus of the control group while having no significant effect in EtOH-exposed rats. Low doses of ALLO (1 and 5 mg/kg) were found to increase motor activity. CONCLUSIONS: These data indicate that a history of EtOH exposure attenuates some of the neurophysiological effects of ALLO in a manner consistent with cross-tolerance. Taken together, these data suggest that increased sensitivity to ALLO's neurobehavioral effects is limited to the early phases of EtOH withdrawal and may not extend to more protracted periods of abstinence.     

Enhanced prepulse inhibition following adolescent ethanol exposure in Sprague-Dawley rats

OBJECTIVES: Recent studies have demonstrated that ethanol exposure differentially affects adolescents and adults. The current studies were designed to compare the effects of 2-week exposure to ethanol during adolescence or adulthood on the acoustic startle response (ASR) and prepulse inhibition (PPI) METHODS: Male Sprague-Dawley rats were exposed to ethanol vapor 12 hr/d (on from 6 pm to 6 am) for 14 days during adolescence or adulthood. Six days after the cessation of ethanol vapor exposure, the ASR and PPI were assessed. RESULTS: During ethanol treatment, overall blood alcohol levels averaged 230 to 250 mg/dl in the adolescent and adult treatment groups. Assessment of the ASR revealed that latency to startle was more rapid in adolescents than in adults, but ASR latency was not altered by ethanol exposure. In addition, ASR magnitude was lower in adolescents and was decreased in ethanol-exposed rats on startle trials. Ethanol exposure significantly enhanced PPI, but only after adolescent exposure CONCLUSIONS: These data further demonstrate a differential sensitivity of adolescents and adults to the effects of ethanol exposure. Specifically, a 2-week period of ethanol exposure during adolescence selectively enhanced PPI, a neurobehavioral index of sensorimotor gating. However, ASR magnitude was decreased by ethanol exposure regardless of age. On the basis of previous studies, the effects of ethanol exposure on PPI data could indicate that adolescent rats exposed to ethanol are more likely to exhibit behavioral inflexibility and that ethanol exposure acts as a more potent physical stressor in adolescent rats.     

Evaluation of the Sheffield system for identifying children at risk from unexpected death in infancy. Results from Birmingham and Newcastle upon Tyne

The "at birth" system which is used in Sheffield to identify children likely to die unexpectedly in infancy, was tested retrospectively in Birmingham (83 cases) and in Newcastle upon Tyne (56 cases). The discrimination between cases and age-matched controls was poor in both cities. Analysis of the 8 factors used in the system showed that only 2 maintained significant case/control differences in Birmingham and Newcastle. Further investigation showed that other factors from maternity records showed significant case/control differences in these cities. Although the system used in Sheffield would not be of use in a prospective prevention programme in either Newcastle or Birmingham, the possibility of evolving an "at risk" system which might apply more widely is discussed.