Different behavioral deficits are induced by anoxia/hypoxia in neonatal and senescent rats: blockade by MK-801

Rats exposed on their first postnatal day to 100% nitrogen for 25 min developed hyperactivity and lower performance in passive avoidance task during development. Administration of MK-801 (0.5 mg/kg i.p.) 1 h before anoxia or (0.25 and 0.5 mg/kg) 1 h after completely reversed this behavioral impairment. Senescent rats (24-26 months) exposed to hypoxia (92% N2 + 8% O2) for 5 h failed in their performance in C.A.R., 30 days later. Pretreatment with MK-801 (1 mg/kg i.p.) completely reversed this impairment. These data suggest that activation of endogenous NMDA receptors produces different behavioral consequences in neonatal and senescent rats and that MK-801 administration close to exposure of animals to anoxia or hypoxia can prevent such damage, thus preventing behavioral impairments in postnatal as well as in senescent rats.     

Functional recognition of the neuronal tyrosine hydroxylase cAMP regulatory element in different cell types.

Transient transfection of pLB2CAT constructs bearing short synthetic oligonucleotides derived either from the tyrosine hydroxylase (TH) promoter or other sources was used to examine functional cAMP regulatory element (CRE) activity in a variety of cell lines. The region containing only the putative TH CRE was found to be as or more effective in conferring cAMP responsiveness onto pLB2CAT (which employs the TK promoter) than the immediate 272 bp region of the TH promoter. Increases in CAT activity of 10- to 20-fold were observed in JEG-3 cells with a single insert of the TH CRE region (-31 to -54) in pLB2CAT, and the presence of a second insert generated only a modest further increase. This construct also responded to cAMP in 4 other cell lines tested but the degree of increase was less dramatic. Inserts containing the consensus 8 bp CRE motif embedded in other natural or artificial contexts served generally as weak functional CREs in all cell lines tested. In vitro analysis revealed that a specific protein-DNA complex apparently containing a single protein with a MW of 45-50 kDa was formed equally well with JEG-3 cell nuclear extract and CRE-bearing-TH and other fragments which produced dramatically different cAMP effects in vivo. These results suggest specificity in the effects of cAMP on different CREs which are dictated by contextual differences.     

Response to treatment in panic disorder with associated depression

Thirty outpatients with panic disorder (PD) were treated at an anxiety clinic using a symptom-focused approach. Thirteen (43%) had no history of major depressive disorder (MDD), 12 (40%) had a history of secondary MDD, and 5 (17%) had history of primary MDD. The outcome was equally good in patients with no history of MDD (77% had good or excellent outcomes) and patients with a history of secondary MDD (83% had good or excellent outcomes). Patients with a history of primary MDD had the worst outcomes. These findings agree with earlier studies showing that secondary MDD does not adversely affect prognosis of patients presenting for treatment of PD.     

Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo: effects of median forebrain bundle stimulation frequency, stimulation pattern, and dopamine autoreceptors

In vivo microdialysis coupled with HPLC and radioimmuno-assay techniques were used to analyze dopamine (DA) and neurotensin (NT) in prefrontal cortical extracellular fluid following electrical stimulation of mesocortical axons. The release (overflow into the extracellular fluid) of both DA and NT increased with increasing number of impulses and with frequency. At the lowest frequency tested (2.5 Hz), DA release was significantly increased, while there was no significant increase in the release of NT. As the frequency of stimulation was increased from 2.5 to 20 Hz, the ratio of extracellular DA:NT decreased exponentially. Stimulation in a burst pattern produced greater release of both DA and NT than tonic stimulation when the number of impulses per second and the total number of impulses were held constant. Furthermore, blockade of DA autoreceptors with sulpiride stereoselectively increased the release of DA while decreasing the release of NT. These data suggest that the release of coexistent molecules (DA and NT) from mesocortical neurons can be influenced by physiological and pharmacological factors such that under certain conditions simultaneous or differential release may occur.     

The effects of hyponatraemia and subarachnoid haemorrhage on the cerebral vasomotor responses of the rabbit

Impairment of cerebral autoregulation and development of hyponatraemia are both implicated in the pathogenesis of delayed cerebral ischaemia and infarction following subarachnoid haemorrhage (SAH) but the pathophysiology and interactions involved are not fully understood. We have studied the effects of hyponatraemia and SAH on the cerebral vasomotor responses of the rabbit. Cerebrovascular reactivity to hypercapnia and cerebral autoregulation to trimetaphan-induced hypotension were determined in normal and hyponatraemic rabbits before and 6 days after experimental SAH produced by two intracisternal injections of autologous blood. Hyponatraemia (mean plasma sodium of 119 mM) was induced gradually over 48 h by administration of Desmopressin and intraperitoneal 5% dextrose. Sham animals received normal saline. The cerebrovascular reactivity (% change +/- SD in cortical CBF/mm Hg PaCO2, measured by hydrogen clearance) of hyponatraemic (4.8 +/- 3.0%) and SAH (1.3 +/- 2.0%) animals was significantly less (p less than 0.05) than control (11.6 +/- 4.0%) and sham (8 +/- 2.0%) animals, whereas the reactivity of hyponatraemic-SAH animals was preserved (9.8 +/- 6.0%). Hyponatraemia and SAH alone each significantly impaired CBF autoregulation but their combined effects were not additive. Systemic hyponatraemia impairs normal cerebral vasomotor responses but does not augment the effects of experimental SAH in the rabbit.     

The effect of age, sex, weight and height on the plasma concentrations in healthy subjects of the acidic metabolites of some biogenic monoamines involved in psychiatric and neurological disorders.

1. The plasma concentrations of unconjugated phenylacetic acid and m-hydroxyphenylacetic acid are lower in male than in female subjects. 2. The plasma concentrations of unconjugated phenylacetic acid and mandelic acid decrease with increasing weight and height for all subjects combined. The same relationships apply for both males and females but are significant only for males. 3. Homovanillic and vanillylmandelic acid concentrations in plasma increase with age. 4. The importance of using age, sex, weight and height matched groups in studies involving the plasma concentrations of some of the trace amine metabolites in psychiatric disorders has been demonstrated. This is particularly the case for phenylacetic acid, the major metabolite of phenylethylamine which is now thought to be a neuromodulator of catecholaminergic neurotransmission.     

Treatment with methylazoxymethanol at different gestational days: physical, reflex development and spontaneous activity in the offspring

Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational day 14, 15, 16, 17, 18 or 19 and offspring were tested for their physical development, reflex development and spontaneous activity. MAM treatment did not affect gestational and litter parameters at any of the time of administration studied. Treatment at gestational day 14 (GD14) had the most severe effect on functional neurodevelopment until weaning: righting reflex at surface, chimney test, horizontal wire test resulted altered. Administration at GD15, 16, 18, 19 did not affect the performance in these tests. Offspring treated at GD17 showed a delayed eye opening and an impaired performance in the horizontal wire test. When tested at 50 days of age on the rotarod, all the treated groups performed worse than controls with the exception of GD19 treated offspring. Administration at GD14 and GD15 resulted in increased spontaneous activity of the offspring at 21 days but not at 60 days of age. Different degrees of microencephaly were observed for all treated groups. The results indicate that alterations of physical and behavioral development induced by MAM treatment are dependent on the time of MAM administration, and specific behavioral tests are able to detect different abnormalities and differentiate among treatment groups. Some alterations observed in MAM rats undergo to adaptive changes during maturation of the CNS.     

The identity of the calcium-storing, inositol 1,4,5-trisphosphate-sensitive organelle in non-muscle cells: calciosome, endoplasmic reticulum ... or both?

Although the initial phase of receptor-mediated Ca2+ signaling, involving Ca2+ release from intracellular stores by inositol 1,4,5-trisphosphate, is relatively well characterized, the nature of the organelle releasing Ca2+ is a controversial subject. At issue is the question of whether Ca2+ is released from the endoplasmic reticulum, or from a more specialized organelle called the 'calciosome'. In this review, we attempt to analyse the arguments for and against these two views, and attempt to reconcile some of the apparently conflicting findings by proposing a hypothetical model of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool.