Effect of long-term ethanol feeding on brainstem α2-receptor binding in Wistar–Kyoto and spontaneously hypertensive rats

Our previous studies have shown that ethanol attenuates baroreflex function in Wistar–Kyoto (WKY) but not in spontaneously hypertensive rats (SHRs). The present study determined the effects of chronic ethanol administration on α₂-binding sites in brainstem areas that modulate baroreflexes. In vitro autoradiography was utilized to evaluate the effect of a 3-month ethanol feeding on the density (B_max) and affinity (K_D) of α₂-adrenoceptors in the middle (mNTS) and rostral (rNTS) portions of the nucleus tractus solitarius of SHRs and WKY rats. Autoradiographic examination of brainstem sections preincubated with [¹²⁵I]p-iodoclonidine revealed no inter-strain differences in α₂-binding in control rats. Ethanol feeding caused strain-dependent changes in α₂-binding activity, which comprised significant (P<0.05) decreases in the density of α₂-binding sites in both areas of the NTS in SHRs versus no effect in WKY rats. These findings do not favor a role for brainstem α₂-adrenoceptors in ethanol-induced attenuation of baroreflexes. Interestingly, the ethanol-evoked reduction in the NTS α₂-receptor density in SHRs may explain reported findings that ethanol abolishes the hypotensive effect of the α₂-adrenoceptor agonist clonidine in this rat model.     

Parabrachial nucleus involvement in multiple system atrophy

Multiple system atrophy (MSA) is associated with respiratory dysfunction, including sleep apnea, respiratory dysrhythmia, and laryngeal stridor. Neurons of the parabrachial nucleus (PBN) control respiratory rhythmogenesis and airway resistance. Objectives: The objective of this study is to determine whether there was involvement of putative respiratory regions of the PBN in MSA. Methods: We examined the pons at autopsy in 10 cases with neuropathologically confirmed MSA and 8 age-matched controls. Sections obtained throughout the pons were processed for calcitonin-gene related peptide (CGRP) and Nissl staining to identify the lateral crescent of the lateral PBN (LPB) and the Kölliker-Fuse nucleus (K-F), which are involved in respiratory control. Cell counts were performed using stereology. Results: There was loss of CGRP neurons in the PBN in MSA (total estimated cell counts for the external LPB cluster was 12,584 ± 1146 in controls and 5917 ± 389 in MSA, p < 0.0001); for the external medial PBN (MPB) cluster it was 15,081 ± 1758 in controls and 7842 ± 466 in MSA, p < 0.001. There was also neuronal loss in putative respiratory regions of the PBN, including the lateral crescent of the LPB (13,039 ± 1326 in controls and 4164 ± 872 in MSA, p < 0.0001); and K-F (5120 ± 495 in controls and 999 ± 308 in MSA, p < 0.0001). Conclusions: There is involvement of both CGRP and putative respiratory cell groups in the PBN in MSA. Whereas the clinical implications of CGRP cell loss are still undetermined, involvement of the LPB and K-F may contribute to respiratory dysfunction in this disorder.     

Postnatal changes of nicotinic acetylcholine receptor 2, α3, α4, α7 and β2 subunits genes expression in rat brain

Postnatal changes of nicotinic acetylcholine receptor (nAChR) α2, α3, α4, α7 and β2 subunits mRNAs were investigated in rat brain using ribonuclease protection assay. Multiple developmental patterns were observed: (1) transient expression during the first few postnatal weeks; α2 in the hippocampus and brain stem, α3 in the striatum, cerebellum and cortex, α4 in the hippocampus, striatum and cerebellum, α7 in the cerebellum and β2 in the striatum. (2) Constant expression across development; α2 and α3 in the thalamus, α4 in the cortex, thalamus and brain stem, α7 in the thalamus and brain stem and β2 in all brain regions except striatum. (3) Non-detection across development; α2 in the cortex, striatum and cerebellum. (4) Increase with age; α7 in the cortex and hippocampus. (5) Bell-shaped development; α7 in the striatum. Postnatal changes of nAChR isoforms in different brain regions of rat were investigated by receptor binding assays. The developmental patterns of [³H]epibatidine and (−)-[³H]nicotine binding sites were similar to each other in each brain region, but different from that of [³H]α-bungarotoxin binding sites. No obvious correlation was observed between the developmental patterns of [³H]α-bungarotoxin, [³H]epibatidine and (−)-[³H]nicotine binding sites and corresponding subunits mRNAs. These results indicate that multiple mechanisms are involved in changes of gene expression of nAChRs subunits in the brain of developing rats.     

Hypomyelinated mutant mice. II. Myelination in vitro

Organotypic cultures of cerebellum from hypomyelinated mutant mice provide a powerful experimental system for studying the cell biology of the mutant diseases. We have examined the extent to which the culture system reproduces the diseases of three well-known mutants,qk,jp^msd, andjp.Quantitation of myelin profiles per sq. mm of section demonstrates that in vitro, as in situ,qk produces the most myelin,jp^msd an intermediate amount, andjp the least. Myelin inqk cultures is unique in being invisible by light microscopy of the living culture. Hypomyelination ofjp may be more severe in vitro than in situ. Cultures ofjp^msd exhibit many of the ultrastructural features of cerebellar abnormalities that occur in situ: degree of hypomyelination, clustering of myelin segments, scarcity of oligodendrocytes, absence of nodes of Ranvier but presence of heminodes, and apparent structural integrity of the myelin sheaths. Correspondence between in vitro and in situ ultrastructure is more difficult to assess forjp, because the available sample ofjp myelin in vitro is too small, and forqk, because the abnormalities observed in situ resemble nonspecific abnormalities of normal myelin in vitro.     

Regeneration of myelinated fiber after crush injury is retarded in sciatic nerves of mutant Japanese quails deficient in neurofilaments

Regeneration of myelinated fibers in the sciatic nerve 2 weeks after crush injury was studied morphometrically in mutant Japanese quails deficient in neurofilaments and in normal quails (controls). There were fewer regenerated myelinated fibers per nerve at 10 mm (R₁) and 20 mm (R₂) distal to the crush site in mutants than in controls (P < 0.05). Both median and maximum diameters were smaller (P < 0.01) in mutants than in controls. On electron microscopy, transverse axonal area and axonal circumference were smaller (P < 0.001) at both R₁ and R₂ in mutants than in controls. The number of myelin lamellae was less (P < 0.01) in mutants than in controls at R₁, but was similar at R₂. There were fewer myelin lamellae in relation to axonal area in mutants than in controls at R₁ (P < 0.0001) and R₂ (P = 0.0032). The results indicate a retardation of both radial growth of axons and myelination around axons of the same size in mutants compared with controls. Such retardation may be explained by the deficiency of neurofilaments and the altered relationship between Schwann cell and axon in the mutant. Received: 18 December 1995 / Revised, accepted: 20 May 1996     

Immortalized cell lines for real-time analysis of circadian pacemaker and peripheral oscillator properties

In the mammalian circadian system, cell‐autonomous clocks in the suprachiasmatic nuclei (SCN) are distinguished from those in other brain regions and peripheral tissues by the capacity to generate coordinated rhythms and drive oscillations in other cells. To further establish in vitro models for distinguishing the functional properties of SCN and peripheral oscillators, we developed immortalized cell lines derived from fibroblasts and the SCN anlage of mPer2 ^Luc knockin mice. Circadian rhythms in luminescence driven by the mPER2::LUC fusion protein were observed in cultures of mPer2 ^Luc SCN cells and in serum‐shocked or SCN2.2‐co‐cultured mPer2 ^Luc fibroblasts. SCN mPer2 ^Luc cells generated self‐sustained circadian oscillations that persisted for at least four cycles with periodicities of ≈24 h. Immortalized fibroblasts only showed circadian rhythms of mPER2::LUC expression in response to serum shock or when co‐cultured with SCN2.2 cells. Circadian oscillations of luminescence in mPer2 ^Luc fibroblasts decayed after 3–4 cycles in serum‐shocked cultures but robustly persisted for 6–7 cycles in the presence of SCN2.2 cells. In the co‐culture model, the circadian behavior of mPer2 ^Luc fibroblasts was dependent on the integrity of the molecular clockworks in co‐cultured SCN cells as persistent rhythmicity was not observed in the presence of immortalized SCN cells derived from mice with targeted disruption of Per1 and Per2 (Per1^ldc/Per2 ^ldc). Because immortalized mPer2 ^Luc SCN cells and fibroblasts retain their indigenous circadian properties, these in vitro models will be valuable for real‐time comparisons of clock gene rhythms in SCN and peripheral oscillators and identifying the diffusible signals that mediate the distinctive pacemaking function of the SCN.     

Amyotrophic lateral sclerosis weakens spinal recurrent inhibition and post-activation depression

ObjectivesAmyotrophic lateral sclerosis (ALS) disrupts motoneurons that control movement and some vital functions, however, exact details of the neuronal circuits involved in ALS have yet to be fully endorsed. To contribute to our understanding of the responsible neuronal circuits, we aimed to investigate the spinal recurrent inhibition (RI) and post-activation depression (P-AD) in ALS patients.MethodsIn two groups of ALS patients, i.e. lumbar-affected (clinical signs in leg muscles) and nonlumbar-affected (clinical signs in arms or bulbar region but not in the legs), RI and P-AD on the soleus muscle were investigated using single motor units and amplitude changes of H-reflex in surface electromyography, respectively. The data were compared with healthy subjects.ResultsCompared to controls, P-AD of H-reflex was reduced severely in lumbar-affected patients and reduced to a certain degree in nonlumbar-affected patients. Similarly, a significant reduction in the duration of RI on firing motoneurons was found in lumbar-affected patients (11.5 ± 2.6 ms) but not in nonlumbar-affected patients (29.7 ± 12.4 ms, P < 0.0001) compared to controls (30.8 ± 7.2 ms, P < 0.0001).ConclusionThe current study revealed that spinal inhibitory circuits are impaired in ALS.SignificanceThese findings may provide insight for proposing new therapeutic approaches and following disease progression in humans.     

Increased PrPC expression correlates with endoglin (CD105) positive microvessels in advanced carotid lesions

Normal cellular prion protein (PrP^C) has multiple functions but its role in the development of atherosclerosis has not been studied. Our pilot microarray data showed increased expression of PrP^C in tissue samples of complicated carotid lesions. Therefore in this study, we aimed to investigate its localisation within atherosclerotic arteries and its concentration in patient plasma. PrP^C expression was examined using an enzyme immunometric assay (EIA) in plasma from patients undergoing endarterectomy. Carotid specimens and control vascular transplants were studied for PrP^C and CD105 (endoglin, a marker of active vessels) expression by immunohistochemistry and real-time PCR. Patients with carotid disease had higher levels of plasma PrP^C than the control group [4.35 ng/ml (n = 22; 3.1–5.3) vs. 1.95 ng/ml (n = 21; 1.1–2.5), P < 0.001]. Furthermore, CD105-positive plaques had higher PrP^C expression which colocalized with CD105 in neovessels. There was a significant correlation between mRNA expression of PrP^C and CD105 in tested plaques (P < 0.001; r = 0.7) supporting our immunohistochemical findings. We conclude that PrP^C is expressed in carotid specimens and may be associated with neovessel growth or survival in these plaques. Our results suggest a role for PrP^C in modulating neovessel formation in complicated plaques.     

Physiological levels of β-amyloid induce cerebral vessel dysfunction and reduce endothelial nitric oxide production

Abstract

β-amyloid (Aβ), the major component of senile plaques in Alzheimer's disease (AD), normally circulates in the blood at nanomolar levels but is elevated in AD. Previous studies have found that high concentrations (10^-5 -10^-4 M) of Aβ result in neuronal cell death. Here we show that physiological levels of soluble Aβ can induce dysfunction in perfused rat cerebral vessels and in cultured endothelial cells. At concentrations of 10^-9 -10^-6 M, Aβ induced a significant concentration-dependent reduction of NO production in endothelial cells. At 10^-8 M, Aβ significantly decreased the sensitivity of cerebral vessels to acetylcholine (ACh), an endothelium dependent vasodilator. At 10^-7 M and higher concentrations, Aβ significantly reduced the maximum response of vessels to ACh, and induced significant endothelial cell death. Aβ (10^-9 -10^-5 M) did not cause any detectable change in nitric oxide synthase levels. The results suggest that a modest increase in the concentration of Aβ above its normal physiological level in the circulation, as found in the early stages of AD, results in decreased NO production and vessel sensitivity to endothelium-dependent vasodilation that could lead to constricted blood vessels and ischemia in the surrounding tissue. Further increases in Aβ concentration, which may occur in the later stages of AD, result in cell death and decreased maximum vasodilator response of cerebral vessels. [Neurol Res 2001; 23: 506-512]     

Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration

Amyloid β (Aβ) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer’s disease to determine if intraneuronal Aβ immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Aβ immunoreactivity in neurons in infants and stable neuron-type specific Aβ immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4–13 aa and 8–17 aa of Aβ in neurons indicated that intraneuronal Aβ was mainly a product of α- and γ-secretases (Aβ_17–40/42). The presence of N-terminally truncated Aβ_17–40 and Aβ_17–42 in the control brains was confirmed by Western blotting and the identity of Aβ_17–40 was confirmed by mass spectrometry. The prevalence of products of α- and γ -secretases in neurons and β- and γ-secretases in plaques argues against major contribution of Aβ-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Aβ_17–42 immunoreactivity was observed in structures with low susceptibility to fibrillar Aβ deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Aβ immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Aβ immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Aβ represents a product of normal neuronal metabolism. This study was supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and grants from the National Institutes of Health (The National Institute of Child Health and Human Development R01 HD43960 and PO1 HD35897; and the National Institute of Aging P30 AG08051, AG03051, and PO1 AG11531).     

Cortical release of labeled compounds during arousal in the cat: correlations with carbon dioxide, brain temperature and EEG.

The release of ⁴⁵Ca²⁺, ³H₂O, [¹⁴C]-carboxyl-inulin, [³H]-γ-aminobutyric acid, [¹⁴C]-taurine, [³H]-5-hydroxytryptamine, [³H]-norepinephrine and [³H]-lysine from cerebral cortex into a superfusion medium has been studied in vivo, using locally anesthetized, immobilized cats. Peaks in the rate of release of all these compounds from the suprasylvian gyrus could be correlated with a diminished amplitude of the cortical EEG and with increases in brain temperature and levels of CO₂ in alveolar air. Peaks correlated with pCO₂ could still be observed after the topical application of 5 × 10^?4 NaCN. Death, produced by an overdose of pentobarbital, resulted in a 45% drop in the release of ⁴⁵Ca²⁺ and ³H-GABA followed by irregular peaks in efflux. Superfusion of the cortical surface with a low Ca²⁺ medium resulted in very regular oscillations in the efflux of a number of isotopes including ⁴⁵Ca and ³H₂O. These oscillations, which had a period of about 6 min, were best observed immediately before or after a train of seizures, while the efflux pattern during seizures was slightly more irregular. The ratio of ⁴⁵Ca²⁺ and ³H₂O released at this time also rose and fell in phase with the oscillations in efflux. At each individual seizure, the Ca/³H₂O ratio fell to a minimum. On two occasions marked long term changes in the amplitude of the EEG were observed to correlate with a change in the amplitude of the oscillations. Hemodynamic factors are considered to affect the rate of release of isotopes into the superfusate but cortical metabolism is also likely to play a role in controlling the rate of release, especially during the oscillations in efflux in low calcium media.     

Gender- and age-dependent changes in nucleoside levels in the cerebral cortex and white matter of the human brain

Nucleosides are neuromodulators that participate in various neuronal functions in the brain. In previous studies, we described regional differences in the concentrations of nucleosides and their derivatives in the human brain. To better understand the functions of nucleosides in the central nervous system, we investigated gender- and age-dependent changes in the levels of nucleosides and their metabolites. The concentrations of uridine, inosine, guanosine and adenosine as well as uracil, hypoxanthine and xanthine were measured in the frontal cortex and white matter of post-mortem brain tissue samples of middle-aged and old men as well as women. The average in vivo concentrations calculated from the 40 samples investigated (regardless of anatomical locations, gender or age; mean ± S.E.M.) were as follows (pmol/mg wet tissue weight): 9.7 ± 0.8 adenosine, 85.8 ± 3.9 inosine, 14.3 ± 0.9 guanosine, 37.3 ± 1.8 uridine, 8.9 ± 0.6 uracil, 63.3 ± 2.1 hypoxanthine and 38.7 ± 1.5 xanthine. We conclude that concentration differences between uridine, inosine, guanosine and adenosine in the frontal cortex and cerebral white matter suggest that nucleoside metabolism is altered with aging and regulated differently between men and women.     

How do different diagnostic criteria, age and gender affect the prevalence of attention deficit hyperactivity disorder in adults? An epidemiological study in a Hungarian community sample

The goal of the study was twofold: (1) to investigate the effect of different diagnostic criteria on prevalence estimates of adult attention deficit hyperactivity disorder (ADHD), and (2) to provide prevalence estimates of adult ADHD for the first time in a Hungarian sample. Subjects between 18 and 60 years were included in the screening phase of the study (N = 3,529), conducted in 17 GP practices in Budapest. Adult self-report scale 6-item version was used for screening. Out of 279 positively screened subjects 161 subjects participated in a clinical interview and filled out a self-report questionnaire to confirm the diagnosis. Beside DSM-IV diagnostic criteria, we applied four alternative diagnostic criteria: ‘No-onset’ (DSM-IV criteria without the specific requirement for onset); full/Sx (DSM-IV “symptoms only” criteria); and reduced/Sx (DSM-IV “symptoms only” criteria with a reduced threshold for symptom count). Crude prevalence estimates adjusted for the specificity and sensitivity data of the screener were 1.35% in the ‘DSM-IV’ group, 1.64% in the ‘No-onset’ group, 3.65% in the ‘Sx/full’ group and 4.16% in the ‘Sx/reduced’ group. Logistic regression analysis showed that ADHD was significantly more prevalent with younger age and male gender [χ² = 14.46; P = 0.0007]. Prevalence estimates corrected for the ‘not-interviewed’ subsample and adjusted for specificity and sensitivity data of the screener was 2.3% in males, 0.91% in females; 2.02% in the ≤40 years age group and 0.70% in the >40 years age group, based on DSM-IV diagnostic criteria. Prevalence rates found in this study are somewhat lower, but still are in line with those reported in the literature.     

D2 autoreceptor switches CB2 receptor effects on [3H]-dopamine release in the striatum

CB₂ receptors (CB₂R) are expressed in midbrain neurons. To evidence the control of dopamine release in dorsal striatum by CB₂R, we performed experiments of [³H]-dopamine release in dorsal striatal slices. We found a paradoxical increase in K⁺-induced [³H]-dopamine release by CB₂R activation with GW 833972A and JWH 133 two selective agonist. To understand the mechanism involved, we tested for a role of the D₂ autoreceptor in this effect; because in pallidal structures, the inhibitory effect of CB₁ receptors (CB₁R) on GABA release is switched to a stimulatory effect by D₂ receptors (D₂R). We found that the blockade of D₂ autoreceptors with sulpiride prevented the stimulatory effect of CB₂R activation; in fact, under this condition, CB₂R decreased dopamine release, indicating the role of the D₂ autoreceptor in the paradoxical increase. We also found that the effect occurs in nigrostriatal terminals, since lesions with 6-OH dopamine in the middle forebrain bundle prevented CB₂R effects on release. In addition, D₂–CB₂R interaction promoted cAMP accumulation, and the increase in [³H]-dopamine release was prevented by PKA blockade. D₂–CB₂R coprecipitation and proximity ligation assay studies indicated a close interaction of receptors that could participate in the observed effects. Finally, intrastriatal injection of CB₂R agonist induced contralateral turning in amphetamine-treated rats, which was prevented by sulpiride, indicating the role of the interaction in motor behavior. Thus, these data indicate that the D₂ autoreceptor switches, from inhibitory to stimulatory, the CB₂R effects on dopamine release, involving the cAMP → PKA pathway in nigrostriatal terminals.     

Racial disparities in sleep health between Black and White young adults: The role of neighborhood safety in childhood

ObjectivesBlack adults in the United States have shorter sleep durations and poorer sleep efficiency relative to White adults, yet reasons for these disparities are not well explicated. The objective of this study was to examine neighborhood safety in childhood as a mediator of subsequent racial disparities in sleep.MethodsData were from Black and White young adults attending a large, predominantly White university in the Southeastern United States (N = 263; 52% Black, 53% female; Mean age = 19.21 years, SD = 1.01). Sleep parameters were assessed from eight nights of wrist actigraphy (time in bed, sleep duration, and efficiency) and an established self-report measure of daytime sleepiness. Residential histories from birth through age 18 were documented, and retrospective self-reports of neighborhood safety in childhood were assessed.ResultsBlack participants had less time in bed (p < 0.001), shorter sleep duration (p < 0.001), poorer sleep efficiency (p < 0.001), and more daytime sleepiness (p = 0.009) than White participants. Neighborhood safety mediated race differences in time in bed (p = 0.028), sleep duration (p = 0.033), and daytime sleepiness (p = 0.048), but not sleep efficiency. Findings were substantively unchanged after adjustment for family socioeconomic status, BMI, and substance use.ConclusionsFindings support the hypothesis that neighborhood safety in childhood may partially account for race differences in subsequent sleep duration and daytime sleepiness. Addressing racial inequities in childhood neighborhood safety may be an important step toward reducing racial disparities in sleep health.     

Hypothalamic prostaglandin E2 during lipopolysaccharide-induced fever in guinea pigs

Prostaglandin E₂ (PGE₂) is postulated to be a central mediator of fever. It is generally believed that it is produced in the preoptic area of the anterior hypothalamus (POA) because, among other evidence, its level increases both in the third ventricle and in the POA in response to pyrogens. However, lately, the question has arisen whether PGE₂ might, in fact, be formed outside of the brain substance and then penetrate it, in particular through the organum vasculosum laminae terminalis. If produced outside the brain substance, the peripheral blockade of its synthesis should prevent lipopolysaccharides (LPS)-induced fever, whereas the intracarotid infusion of PGE₂ should produce an increase in core temperature (T_c) as well as in preoptic PGE₂. To verify this hypothesis, continuous measurements of T_c and preoptic PGE₂ levels were made in conscious guinea pigs administered the PGE₂ synthase inhibitor, indomethacin (10 or 50 mg/kg, im) 30 min before S. enteritidis LPS (2 μg/kg, iv) or before PGE₂ microdialyzed into the POA (1 μg/μl at 2μl/min for 2.5 h) and during PGE₂ infused into a carotid artery (1 μg and 10 μg/μl at 2 μl/min for 1 h). LPS induced a biphasic 1.4°C fever that was consistently associated with an increase in the level of PGE₂ in the POA. Indomethacin at 10 mg/kg attenuated the course of the LPS-induced fever and prevented the associated increase in preoptic PGE₂ for 90 min after fover onset; thereafter, PGE₂ was significantly reduced by comparison with controls. Indomethacin at 50 mg/kg completely abolished both the fever and the increased levels of PGE₂ in the POA; the fever induced by PGE₂ microdialyzed into the POA was not affected by indomethacin pretreatment. The intracarotid infusion of PGE₂ produced T_c falls and no increase in preoptic PGE₂ levels. The indomethacin-induced blockade of fever and inhibition of the associated increase in preoptic PGE₂ levels further substaintiates the presumptive link between PGE₂ in the POA and fever caused by LPS. The failure of exogenous PGE₂ infusion to induce increases in T_c and preoptic PGE₂ levels excludes the possibility that PGE₂ formed outside of the brain penetrates the POA and induces fever. Thus, in guinea pigs, the PGE₂ associated with LPS-induced fever may be synthesized in the POA.     

Psychiatric morbidity in 50 juvenile delinquents in Addis Ababa

Summary A study of 50 juvenile delinquents in a Training Centre in Addis Ababa revealed that psychiatrically disturbed children are found in such an institution, while they are conspicuously absent in out-patient populations. The broken family background of these boys did not bear a clear relationship to the presence of psychiatric disorder and appears to be a normal pattern of life in Ethiopia.

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Zusammenfassung Eine Untersuchung von 50 jugendlichen Delinquenten in einem Arbeitslager in Addis Abeba offenbarte, daß sich in einer solchen Institution psychisch gestörte Kinder finden, während sie im ambulanten Patientengut eindeutig fehlen. Der Hintergrund der zerbrochenen Familien dieser Jungen brachte keine klare Beziehung zu gegenwärtigen psychischen Störungen mit sich und scheint eine normale Lebenserscheinung in Äthiopien zu sein.

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Résumé Une étude de 50 jeunes délinquants d'un centre de rééducation à Addis Abeba a montré qu'on trouve des enfants psychiquement perturbés dans une telle institution, alors qu'ils sont absents, de façon frappante, des populations de patients en traitement ambulatoire. On n'a pas pu établir de relation nette entre la présence de troubles psychiatriques et le milieu familial désuni de ces garçons, qui semble être un mode de vie normal en Ethiopie.

     

Naltrexone induces down- and upregulation of δ opioid receptors in rat brain regions

Opioid antagonists such as naltrexone, naloxone, and ICI 174864 induce a transient downregulation of δ opioid receptors prior to upregulation in NG108-15 cells. Here we show that naltrexone can also elicit a transient downregulation of δ₂ opioid receptors preceding upregulation in brain. A 1 h treatment of rats with naltrexone (IP, 10 mg/kg) resulted in lowered ³H-[D-Se²,L-Leu⁵]lenkephalyl-Thr B_max values in hindbrain, but not in striatum, hippocampus, or cortex. The decrease in hindbrain δ₂ receptor density was not accompanied by changes in K_d values, indicating that downregulation rather than receptor blockade occurred. Longer naltrexone treatment (48 h), caused twofold upregulation of δ opioid binding in all four regions. These data suggest that the process of upregulation of δ opioid receptors by antagonists in vivo can entail an initial, transient downregulation.