Biomedical subjects

B A Pappas

Publications and source records attributed to B A Pappas.

At least 37 records · Page 2Linked to original sources

PubMed1992

Enriched environment primes forebrain choline acetyltransferase activity to respond to learning experience.

Weanling rats were raised in an enriched or an impoverished environment. The enriched rats subsequently learned the Morris water maze faster than their impoverished counterparts. The enriched rats, both maze-trained and untrained, showed higher choline acetyltransferase (ChAT) activity in the caudate than did the impoverished, untrained rats. Maze training increased caudate ChAT in impoverished rats. Enriched but not impoverished rats showed increased hippocampal and anterior cortical ChAT activity after maze training. Thus, enrichment causes a long-lasting increase in caudate acetylcholine (Ach) synthesis and it also primes cortex and hippocampus to respond to a training experience with increased Ach synthesis.

Animals↗

PubMed1992

Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats.

Young and aged rats were subjected to cerebrovascular insufficiency (CVI) for 3 and 9 weeks. At the end of each time period, local cerebral blood flow (lCBF), spatial memory function, 31P- and 1H-NMR spectroscopy and imaging of the brains were evaluated in vivo. Morphometric counts of CA1 hippocampal neuron damage and staining for glial fibrillary acidic protein (GFAP) were done post-mortem. Results show that after 3 weeks of CVI, cortical and hippocampal lCBF was significantly reduced in young and aged animals respectively. In addition, young and aged rats at 3 weeks following CVI showed spatial memory deficits in the Morris water maze and elevation of 31P-phosphomonoester as measured by non-invasive NMR spectroscopy. At the same time period, in vivo 1H-microimaging (MRI) of brains showed areas of high signal intensity (suggesting local edema) localized asymmetrically to the right hippocampal region in young and aged CVI rats. Morphometry of the hippocampal CA1 sector at post-mortem confirmed the in vivo MRI changes and demonstrated that a significant percentage of the CA1 pyramidal cells were damaged after CVI. Nine weeks after CVI, hippocampal CBF reductions, spatial memory impairment, spectroscopic-microimaging changes and CA1 sector cell damage continued to be observed in the aged animals but were resolved in the young rat brains. In addition, GFAP immunoreaction progressively increased in the hippocampus of aged rats subjected to CVI for 9 weeks. It is concluded that cognitive, metabolic and morphologic damage was significantly more severe and longer lasting in aged than young rat brain after chronic CVI. The deficits observed in this rat model appear to mimic the early pathology reported in Alzheimer's disease and suggest that the present model could provide fundamental clues relative to the etiology and possible management of this dementia.

Aging↗

PubMed1992

Neonatal brain dopamine depletion and the cortical and behavioral consequences of enriched postweaning environment.

This study investigated the effects of neonatal intraventricular administration of 6-hydroxydopamine (6-OHDA, 15 micrograms total with and without desmethylimipramine pretreatment) on the cortical thickening and behavioral effects of 35 days of enriched postweaning housing (ENR) in the rat. The 6-OHDA treatment depleted cortical dopamine (DA) to about 40% of control. It did not affect the thickness of the cerebral cortex nor did it affect the capacity for the cortex to be thickened by ENR. In addition, it did not alter the superior performance on two spatial water maze tasks that was caused by ENR. Thus, the potential for neurobehavioral plasticity was not changed by neonatal DA depletion. ENR eliminated the spatial learning/memory deficits that were caused by neonatal DA depletion and that were manifested when the rat was raised in standard (impoverished) laboratory conditions. Hence, environmental factors can modulate the cognitive effects of neonatal DA depletion. ENR did not attenuate the hyperactivity of the neonatal DA-depleted rat. This may reflect the subcortical mediation of this behavioral abnormality.

Animals↗

PubMed1992

Alzheimer's disease and feeling-of-knowing for knowledge and episodic memory.

The metamemory (knowledge of the veracity of memories) of moderately impaired Alzheimer's patients was compared to that of aged controls. Despite their profoundly impaired recall of information from both long-term (knowledge) and recent (episodic) memory, Alzheimer's patients were as accurate as controls in assigning confidence ratings related to the probability that their recalls were correct. They were impaired, however, at predicting the likelihood that they would subsequently recognize correct answers (feeling-of-knowing) to knowledge memory questions which they had been unable to recall correctly. Nevertheless, their performance on this task did exceed chance. Thus, the moderately impaired Alzheimer's patient demonstrates intact awareness of the veracity of recall from knowledge and episodic memory but shows impaired feeling-of-knowing for knowledge memory.

Aged↗

PubMed1991

The histopathological, behavioral and neurochemical effects of intraventricular injection of ethylcholine mustard aziridinium (AF64A) in the neonatal rat.

This study investigated the histopathological, behavioral and neurochemical effects of bilateral injection of 2.0, 0.5 and 0.1 nmol/ventricle ethylcholine aziridinium (AF64A) on postnatal day (PND) 2. The rats showed a significant, but non-dose-related reduction of choline acetyltransferase (ChAT) in the hippocampus but not the cerebral cortex or the caudate nucleus when sacrificed on PND 16. No effect on ChAT was found in any region at PND 58. The group given 2 nmol/ventricle were hyperactive and showed a deficit in spatial learning when tested on the Morris water maze at PND 38-43. No such differences were observed for the rats injected with 0.1 or 0.5 nmol/ventricle AF64A. This spatial learning impairment in the 2 nmol group was associated with non-specific tissue damage seen only in animals from this group that were sacrificed at PND 40. This tissue damage was most evident in the left medial frontal cortex, the caudate nuclei and the anterior dorsal hippocampus.

Animals↗

PubMed1990

Neonatal and adult forebrain norepinephrine depletion and the behavioral and cortical thickening effects of enriched/impoverished environment.

Two experiments examined the effects of neonatal or adult intracerebral injections of 6-hydroxydopamine (6-OHDA) on the effects of enriched (ENR) vs. impoverished (IMP) housing conditions. In Expt. 1, neonatal rats received intraventricular injections of 6-OHDA after pretreatment with buproprion to destroy norepinephrine (NE) terminals while lessening damage to dopamine (DA) terminals. The rats were subsequently raised in either enriched or impoverished environments and then tested for their spatial problem-solving ability in an automated Hebb-Williams maze. Littermates did not undergo this testing but were instead assessed for cortical thickness. Despite the substantial depletion of NE in the forebrains of the 6-OHDA-treated rats, they responded to enriched rearing as did the control rats, i.e., they solved the Hebb-Williams problems more efficiently than their impoverished reared counterparts and they showed thicker cortices. In Expt. 2, adult rats received 6-OHDA lesions of the dorsal noradrenergic bundle and were then relegated to enriched or impoverished housing for 42 days. Subsequently, the enriched-housed rats solved the Hebb-Williams mazes more efficiently than their impoverished-housed counterparts and this effect of housing was not altered by the dorsal bundle lesion which severely depleted forebrain NE. These two experiments do not support a role for forebrain NE in the alteration of the rat cortex and behavior by environmental enrichment. It was concluded that the cognitive effects of enriched rearing do not require intact forebrain NE but that they may be influenced by the peripheral sympathectomy that is one consequence of neonatal systemic 6-OHDA injections.

Animals↗

PubMed1990

Neonatal 6-hydroxydopamine alters the behavior of enriched-impoverished rats in a novel test environment.

The hypothesis that neonatal norepinephrine (NE) depletion lessens the behavioral consequences of differential housing was tested. Male Wistar rats were injected with 6-hydroxydopamine (6-OHDA) or vehicle twice within 24 hr of birth, weaned at 25 days, and reared under either impoverished (IC) or enriched conditions (EC) for 30 days. In 3 experiments, rats were tested in the Morris water maze, the colony-intruder test, and 2 tests of dominance. 6-OHDA treatment reduced cortical and hypothalamic NE concentrations and increased brainstem NE concentrations. EC housing increased cortical dopamine (DA). Behavioral differences caused by postweaning enrichment-isolation were reduced by neonatal NE depletion, primarily in early test trials. The authors conclude that forebrain NE afferents from the locus coeruleus are important for housing-related behavioral changes and responsivity to novel testing environments.

Agonistic Behavior↗

PubMed1989

Noradrenergic and serotonergic mediation of the locomotor and antinociceptive effects of clonidine in infant and adult rats.

This experiment examined the necessity for intact noradrenergic and serotonergic function for the locomotor and nociceptive effects of clonidine in 10- and 100-day-old rats. Newborn rats were administered systemically 6-hydroxydopamine (100 micrograms/g; 12 and 24 hours after birth) to deplete norepinephrine (NE), and at 10 or 100 days they were injected with para-chlorophenylalanine (300 mg/kg PCPA; 5 and 24 hours before testing) to deplete serotonin (5-HT). They were then tested for the locomotor and analgesic effects of one of various clonidine doses (0, 10, 100 or 1000 micrograms/kg). Clonidine enhanced locomotion at 10 days. This effect was potentiated by NE depletion and reduced by 5-HT depletion. Clonidine reduced locomotion at 100 days, and again this was augmented by NE depletion but reduced by 5-HT depletion. NE depletion did not have an enduring effect on clonidine antinociception whereas 5-HT depletion reduced it at both ages. It is concluded that the locomotor effects of clonidine in both infant and adult rats, despite reversing with maturation, reflect its agonist action at postsynaptic alpha2 adrenoceptors. The results also add to the accumulating evidence for an early maturing and behaviorally relevant serotonergic system(s).

Animals↗

PubMed1988

A behavioral and electrocorticographic comparison of diazepam and pentylenetetrazol in rat pups.

This experiment assessed the possibility suggested by previous research that benzodiazepines cause convulsions in infant rats. Seven-day-old Wistar rats were randomly assigned to receive either diazepam (DZP) (0, 0.5 or 2.5 mg/kg), the convulsogen pentylenetetrazol (PTZ) (50 mg/kg), or DZP followed 30 minutes later by PTZ. The amount of paddling and wall progression and head and body tremors was recorded for each group. Both DZP and PTZ elevated paddling and wall progression, but only PTZ elevated head and body tremor scores. DZP antagonized the PTZ-induced increases in head and body tremors. In a second experiment, seven-day-old pups were implanted with cortical electrodes. The following day, baseline electrocorticograms (ECoGs) were taken for each animal. Each pup subsequently received either DZP vehicle, 0.5 mg/kg DZP, 50 mg/kg PTZ, or 0.5 mg/kg DZP followed 30 minutes later by 50 mg/kg PTZ. Neither the vehicle nor the DZP injections altered ECoG activity. In contrast, PTZ-treated pups showed continuous, high-amplitude, spiking activity. Pretreatment with DZP eliminated these PTZ-induced alterations in ECoG activity. We conclude that in infant rats, the behavioral and electrophysiological effects of DZP and PTZ are distinct from one another. Furthermore, both the behavioral and the electrocorticographic effects of PTZ are blocked by DZP. It is unlikely that DZP causes seizures in neonatal rats.

Animals↗

PubMed1987

Forebrain norepinephrine and neurobehavioral plasticity: neonatal 6-hydroxydopamine eliminates enriched-impoverished experience effects on maze performance.

Newborn male rats were depleted of forebrain norepinephrine (NE) by systemic 6-hydroxydopamine injection and then reared from 25 to 60 days under either isolated or enriched conditions. They were subsequently tested for acquisition of either the Lashley III maze or the Hebb-Williams maze problems. Isolated rearing impaired Lashley maze performance of the controls but not the 6-OHDA injected rats. Similarly, for the Hebb-Williams maze, the isolation-reared controls made more errors than their enriched-reared counterparts while no differences were observed between the isolated and enriched reared, 6-OHDA injected rats. These results are consistent with the hypothesis that forebrain NE is permissive to the deleterious behavioral consequences of restricted experience during maturation.

Animals↗

PubMed1987

Neonatal 6-hydroxydopamine lesion of spinal noradrenergic terminals: nociception, clonidine analgesia and spinal alpha two adrenoceptors.

Newborn rats received intraspinal injections of 6-hydroxydopamine to enduringly deplete spinal norepinephrine (NE). When tested in adulthood for pain sensitivity with a hot water-tail immersion procedure, this neonatal spinal NE lesion lowered tail flick latencies of females but not males. It was postulated that this sexually dimorphic sparing or recovery of function reflected the development of denervation supersensitivity for males but not females. Contrary to expectation from such an hypothesis, females, not males, showed exaggerated sensitivity to the analgesic effects of a test dose of clonidine. Furthermore, neither males nor females showed an increased number of spinal cord binding sites for (3H)para-amino-clonidine [(3H)PAC]. These receptor binding data failed to indicate proliferation of the spinal alpha two adrenoceptor in either sex. That the lesioning of spinal NE terminals did not reduce (3H)PAC binding sites suggests that the spinal alpha two adrenoceptor does not reside exclusively on NE terminals. This is consistent with current conclusions concerning the alpha two adrenoceptor in the cerebral cortex.

Adrenergic Fibers↗

PubMed1986

Neonatal 6-hydroxydopamine lesion of forebrain norepinephrine does not eliminate critical period for behavioral effects of gonadal hormone manipulation.

Newborn rats were injected s.c. with 6-hydroxydopamine to deplete forebrain norepinephrine (NE) or with the vehicle. The males were then castrated at 4 days and the females injected with testosterone at 5 days of age. Both sexes were tested for female-like sexual responsiveness to a stud male at 6 months of age. The loss of forebrain NE did not prevent the feminization of the males due to castration or the masculinization of the females due to testosterone. This result contraindicates a general permissive-requisite role for forebrain NE for the mammalian brain's plasticity during its critical periods.

Animals↗

PubMed1985

Neonatal 6-hydroxydopamine potentiates clonidine's locomotor effects throughout maturation in the rat.

Newborn rats were administered 6-hydroxydopamine (6-OHDA) systemically (2 X 100 micrograms/g) or vehicle and subsequently tested for their locomotor response to one of three doses of clonidine (10, 100 or 1000 micrograms/kg) at either 10, 20, 30 or 50 days of age. Clonidine caused a dose-related increase in activity in 10-day-old rats and this effect was potentiated in the 6-OHDA-treated rats. At 20 days, clonidine did not affect activity in the vehicle rats but at the highest dose, increased that of the 6-OHDA rats. At 30 days, clonidine again did not affect activity in the vehicle rats but the 1000 micrograms/kg (when compared to the 100 micrograms/kg) dose, significantly increased activity of the 6-OHDA rats. A biphasic effect of clonidine was apparent at 50 days. At this age the 6-OHDA treatment exaggerated the depressant effect of the 100 micrograms/kg dose. Thus, neonatal-OHDA generally potentiated the locomotor response to clonidine despite the fact that the effect of the drug changed with age. It is concluded that the locomotor effects of clonidine are mediated through alpha 2 adrenoceptors which are not located on noradrenergic terminals but rather are postsynaptic to them. With maturation, the "functional wiring" of these terminals appears to be altered.

Aging↗

PubMed1985

Neonatal 6-hydroxydopamine lesion of spinal norepinephrine terminals fails to affect the ontogeny of swimming behavior.

Newborn rats were injected either systemically or intraspinally with 6-hydroxydopamine. Both treatments drastically reduced spinal norepinephrine (NE), while the former also reduced forebrain NE. Spinal NE loss did not affect the ontogeny or the adult expression of swimming, a sensitive test of complex patterned locomotion. Spinal NE is not essential to either the ontogeny of complex motor behavior or to the generation of such behavior in adult rats.

Animals↗

PubMed1985

Relationship between levels and uptake of serotonin and high affinity [3H]imipramine recognition sites in the rat brain.

High affinity [3H]imipramine binding, endogenous levels of serotonin and noradrenaline, and serotonin uptake were determined in brain regions of rats with selective destruction of serotonergic neurons by 5,7-dihydroxytryptamine (5,7-DHT), of adrenergic neurons by 6-hydroxydopamine (6-OHDA), and of rats treated with reserpine. Neonatal treatment with 5,7-DHT resulted in a significant decrease of both serotonin levels and density (Bmax) of high affinity [3H]imipramine binding sites in the hippocampus. In contrast, an elevation of serotonin levels and an increase in Bmax of [3H]imipramine binding were noted in the pons--medulla region. No changes were observed in the noradrenaline content in either of these regions. Intracerebral 6-OHDA lesion produced a drastic suppression of noradrenaline levels in cerebral cortex but failed to alter the binding affinity (KD) or density (Bmax) of [3H]imipramine recognition sites. A single injection of reserpine (2.5 mg/kg) resulted in marked depletion of both serotonin (by 57%) and noradrenaline (by 86%) content and serotonin uptake (by 87%) in the cerebral cortex but had no significant influence of the parameters of high affinity [3H]imipramine binding in this brain region. The results suggest that high affinity [3H]imipramine binding in the brain is directly related to the integrity of serotonergic neurons but not to the magnitude of the uptake or the endogenous levels of the transmitter, and is not affected by damage to noradrenergic neurons or by low levels of noradrenaline.

5,7-Dihydroxytryptamine↗

PubMed1984

Neonatal 6-hydroxydopamine prevents adaptation to chemical disruption of the pituitary-adrenal system in the rat.

Three days after the subcutaneous implant of a dexamethasone pellet, which depletes both corticosterone and ACTH, normal rats showed impaired acquisition of a two-way avoidance task. Rats who had received systemic 6-hydroxydopamine at birth to lesion the forebrain noradrenergic terminals from the locus coeruleus did not show this impairment. After a single injection of metyrapone, which inhibits corticosterone synthesis and increases ACTH release, both intact and norepinephrine (NE)-depleted rats showed impaired avoidance acquisition. After the seventh injection, however, acquisition in normal rats was no longer impaired by the drug while the NE-depleted rats were still deficient. These results indicate that the simple combination of forebrain NE loss with reduced corticosterone levels does not necessarily retard avoidance acquisition. Rather, they suggest that the NE efferents from the locus coeruleus are essential for the brain's adaptation to at least some behavioral consequences of changes in the circulating level of ACTH.

Adrenocorticotropic Hormone↗

PubMed1984

Deficits in conditioned avoidance responding following adrenalectomy and central norepinephrine depletion are dependent on postsurgical recovery period and phase of the diurnal cycle.

Rats that had undergone combined dorsal noradrenergic bundle lesion (DNBL) and bilateral adrenalectomy were impaired in acquiring a conditioned avoidance response when tested 1 week following surgery. Normal acquisition was observed, however, when testing occurred 3 weeks or more after surgery despite low levels of both plasma corticosterone and brain norepinephrine at that time. Furthermore, neither neonatal systemic administration of 6-hydroxy-dopamine to deplete forebrain norepinephrine, combined with the corticosterone inhibitor metyrapone, nor the pharmacological blockade of noradrenergic receptors, combined with adrenalectomy, disrupted acquisition of the avoidance response. Thus, the combination of forebrain norepinephrine loss and low plasma corticosterone does not inevitably impair avoidance acquisition. Rather, the determining factor for such impairment seems to be the interval between surgery and testing. The impairment at 1 week following DNBL and adrenalectomy occurred only for rats tested during the dark phase of their light cycle. In addition, the DNBL abolished the effect of the light/dark cycle on posttraining plasma corticosterone. These results demonstrate the importance of the phase of the rat's diurnal rhythm on both the hormonal and the behavioral effects of altering the pituitary-adrenal axis and/or forebrain norepinephrine. Because adrenocorticotropin, corticosterone, and vasopressin all show diurnal patterns of release, it cannot be determined at this time which, if any, of these hormones is most important for the behavioral results reported here.

Adrenal Cortex Hormones↗

PubMed1983

Neonatal 6-hydroxydopamine attenuates the neural and behavioral effects of enriched rearing in the rat.

Newborn male rats were administered subcutaneous 6-hydroxydopamine (6-OHDA) to deplete forebrain norepinephrine and after weaning were reared in normal or enriched environments. Subsequently the 6-OHDA treated rats and their vehicle controls were trained in a Lashley type III maze and then sacrificed for assay of regional brain weights and brain catecholamines. Whereas for the control rats, enriched rearing was found to: (1) increase hypothalamic and posterior cortical dopamine; (2) increase forebrain and decrease hypothalamic weight; and (3) to enhance maze acquisition, none of these consequences of enriched rearing was found in the 6-OHDA treated rats. We conclude that forebrain norepinephrine plays a permissive role in the neuroanatomical, neurochemical and behavioral alterations induced by the enriched rearing of weanling rats and that it is essential to at least some aspects of the shaping of the brain by experiential factors.

Animals↗