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Biomedical subjects

F E Bloom

Publications and source records attributed to F E Bloom.

At least 271 records · Page 15Linked to original sources
PubMed1982

Effects of chronic lithium treatment on dopamine receptors in the rat corpus striatum. I. Locomotor activity and behavioral supersensitivity.

Spontaneous locomotor activity and dopaminergic responsivity were assessed after long-term dietary treatment with the anti-manic drug lithium. Chronic dietary Li administration was not accompanied by the toxicities often reported with other modes of administration. In addition, the diet reliably yields serum and brain Li levels in the prophylactic range for manic-depressive illness. After 4 weeks exposure to Li, spontaneous locomotor activity was reduced as compared to subjects on the control diet whether or not food intake was restricted. The depression of locomotor activity following an injection of the dopamine agonist, apomorphine, was less severe in animals that ingested Li compared to those with free access to the control diet. Finally, in confirmation of the findings of Pert et al., chronic Li administration led to a partial attenuation of apomorphine-evoked stereotyped behaviors in subjects rendered supersensitive to the drug by daily injections of haloperidol (HAL) for 3 weeks. The findings suggest that the commonly reported suppressant action of Li on spontaneous behavior is not attributable to overt toxicity or to diminished growth rate. Similarly, these health factors do not account for the ability of chronic Li treatment to suppress the behavioral manifestation of dopaminergic supersensitivity associated with long-term HAL exposure.

Animals↗
PubMed1982

Effects of chronic lithium treatment on dopamine receptors in the rat corpus striatum. II. No effect on denervation or neuroleptic-induced supersensitivity.

The influence of chronic dietary lithium administration was evaluated on dopamine receptor supersensitivity in the rat corpus striatum. Supersensitivity was induced with either unilateral destruction of dopamine-containing fibers in the nigrostriatal pathway or with 3 weeks of treatment with haloperidol (HAL). Both treatments elevated [3H]spiroperidol binding sites, but in neither case was this increase in ligand binding affected by chronic dietary Li (brain levels 0.8 to 1.2 mEq/1 tissue). Our rats receiving 21 daily injections of HAL did show a behavioral supersensitivity to the dopamine agonist, apomorphine, and this effect was attenuated by concurrent treatment with dietary Li (accompanying paper). However, in contrast to previous data, this behavioral attenuation could not be linked to the prevention of increased [3H]spiroperidol binding in the corpus striatum. Furthermore, co-administration of dietary Li to subjects injected with HAL for 3 weeks did not reverse the increased density of [3H]spiroperidol binding sites which developed in the corpus striatum. Neither HAL nor Li treatment altered the affinity of the radioligand for its binding site. In the same animals, neostriatal dopamine-sensitive adenylate cyclase was not affected by either long-term dietary Li or chronic neuroleptic treatment, supporting the view that membrane antagonist and agonist sites differentially adapt to chronic alterations of synaptic input. Taken together, the results are incompatible with the hypothesis that the anti-manic action of Li is related to its ability to prevent dopamine receptor supersensitivity.

Adenylyl Cyclases↗
PubMed1982

Heroin and cocaine intravenous self-administration in rats: mediation by separate neural systems.

The hypothesis that separate neural systems mediate the reinforcing properties of opiate and psychomotor stimulant drugs was tested in rats trained to lever-press of IV injections of either cocaine or heroin during daily 3-h sessions. Pretreatment with the opiate receptor antagonist drug naltrexone produced dose-dependent increases in heroin self-administration, but had no effect on the rate or pattern of cocaine self-administration. Similarly, pretreatment with low doses of the dopamine antagonist drug alpha-flupenthixol produced dose-dependent increases in cocaine but not heroin self-administration. High doses of alpha-flupenthixol eliminated all responding for cocaine and slightly reduced heroin self-administration. The specificity with which the two antagonist drugs exerted their behavioral effects strongly suggests that independent neural substrates are responsible for the reinforcing actions of heroin and cocaine.

Animals↗
PubMed1982

Ethanol and some tetrahydroisoquinolines alter the discharge of cortical and hippocampal neurons: relationship to endogenous opioids.

The activity of single neurons in rat cortex or hippocampus (HPC) was recorded to test two hypotheses: (1) neuronal effects of ethanol are mediated by an endogenous opiate-like mechanism (for example, by release of an endogenous opioid peptide), and; (2) ethanol-induced formation of aldehyde-catecholamine condensation products (tetrahydroisoquinolines; TIQs) might contribute to some acute actions of ethanol. Ethanol and all TIQs were applied to single neurons from multibarrel micropipettes by electroosmosis or pressure. Ethanol most often inhibited neurons of the parietal cortex, while activating most HPC pyramidal neurons. Tetrahydropapaveroline (THP) most often inhibited the spontaneous and glutamate- or acetylcholine (ACh)-induced firing of neurons in both these regions, although some excitations were also seen. In contrast, salsolinol and 7-O-methyl-salsolinol predominantly excited HPC pyramidal neurons, but depressed most parietal cortical neurons. Iontophoretic or SC naloxone usually antagonized the excitatory actions of ethanol, salsolinol and methionine5-enkephalin on HPC pyramidal cells; however, ACh-induced speeding also was antagonized occasionally. Conversely, the antimuscarinic agent scopolamine antagonized the excitatory actions of salsolinol, but not those of met-enkephalin, in some HPC pyramidal cells. These results and those of previous studies show that acutely applied ethanol or salsolinol elicits a region-specific pattern of neuronal effects in brain similar to that previously described for opiates: activity is inhibited in several tested brain areas but excited in hippocampus. Furthermore, these excitatory effects are antagonized by naloxone. However, because of the occasional apparent non-specific effects of naloxone and the puzzling antagonism of the salsolinol-induced excitations by scopolamine, some doubt remains whether the opiate-like actions of these substances can be completely attributed to mediation by opiate receptors.

Animals↗
PubMed1982

Changes in locomotor response to beta-endorphin microinfusion during and after opiate abstinence syndrome--a proposal for a model of the onset of mania.

Beta-Endorphin (0.3 or 0.6 nanomoles) was infused into the A10-ventral tegmental area (VTA) of male Wistar rats previously treated for 6 days with either morphine sulfate or lactose via subcutaneously implanted silastic pellets. Beta-Endorphin microinfusions occurred at 24 and 96 hours after pellets were removed. Profound changes in locomotor response to beta-endorphin were found, with morphine-pretreated rats showing a spontaneous switch from hyporesponsiveness to hyperresponsiveness over 72 hours, compared to lactose-pretreated controls. These findings may reflect on current biochemical theories regarding the "switch" process in bipolar affective disease. The data can be viewed within a heuristic model of receptor changes which may underlie the transition from depression to mania.

Affective Disorders, Psychotic↗
PubMed1982

Arginine vasopressin deficient Brattleboro rats fail to develop tolerance to the hypothermic effects of ethanol.

We have tested the hypothesis that animals with reduced levels of arginine vasopressin (AVP) would show reduced tolerance to ethanol. Brattleboro rats either heterozygous or homozygous for the diabetes insipidus (DI) trait and normal Sprague-Dawley rats were exposed to ethanol vapor for 21 days. Two days later, tolerance was evaluated by monitoring body temperature reductions after intraperitoneal injection of 2 g/kg (20% w/v) ethanol. Under the same conditions of chronic ethanol exposure, Sprague-Dawley rats, but not Brattleboro rats, displayed tolerance to the hypothermic effects of intraperitoneal ethanol. This phenomenon did not appear to be related to differences in ethanol metabolism or blood alcohol levels in Brattleboro rats. These data support a possible role for AVP in the development or maintenance of tolerance.

Animals↗
PubMed1982

beta-Endorphin enhances lymphocyte proliferative responses.

The opioid peptides alpha- and beta-endorphin and [D-Ala2, Met5]enkephalin were investigated for their effect on the proliferation of resting and activated rat splenic lymphocytes in vitro. beta-Endorphin enhanced the proliferative response of spleen cells to the T cell mitogens concanavalin A and phytohemagglutinin. The effect of beta-endorphin was dose dependent and occurred at peptide concentrations similar to those found in rat plasma. alpha-Endorphin and [D-Ala2, Met5]enkephalin did not affect the proliferative responses to any mitogen tested. Furthermore, the potentiating effect of beta-endorphin was not reversed by treatment with 10 microM naloxone. None of the peptides had any effect on resting, unstimulated spleen cells or on the response to a mixture of lipopolysaccharide and dextran sulfate, which is specifically mitogenic for B lymphocytes. The pharmacological properties of the beta-endorphin potentiation indicate that the effect may be mediated by a nonopiate but beta-endorphin-specific mechanism. These results suggest a possible role for peripheral beta-endorphin and may provide a link between stress and disease susceptibility.

Analgesics↗
PubMed1982

Common 82-nucleotide sequence unique to brain RNA.

Several randomly selected cDNA clones made from rat brain polyA+RNA have unusual properties. Although the cDNA inserts are 500-1,250 base pairs long, they hybridize to a 160-nucleotide RNA species that is present in brain but not in liver or kidney. Nucleotide sequence studies of two of the clones and hybridization studies show that a common 82-nucleotide sequence is responsible for the hybridization. The same sequence is located in the second intron of a rat growth hormone gene. These studies suggest that signals called "ID sequences" may be carried in the introns of genes and prescribe their tissue-specific expression.

Base Sequence↗
PubMed1982

Noradrenergic and serotonergic fibers innervate complementary layers in monkey primary visual cortex: an immunohistochemical study.

Antisera directed against human dopamine beta-hydroxylase or serotonin were used to characterize the noradrenergic and serotonergic innervation patterns within the primary visual cortex of the squirrel monkey. The noradrenergic and serotonergic projections exhibit a high degree of laminar complementarity: layers V and VI receive a dense noradrenergic projection and a very sparse serotonergic projection, whereas layer IV receives a very dense serotonergic projection and is largely devoid of noradrenergic fibers. In addition, the noradrenergic fibers manifest a geometric order that is not so readily apparent in the distribution of serotonergic fibers. These patterns of innervation imply that the two transmitter systems affect different stages of cortical information processing--the raphe-cortical serotonergic projection preferentially innervates the spiny stellate cells of layers IVa and IVc, whereas the ceruleo-cortical noradrenergic projection innervates pyramidal cells.

Animals↗
PubMed1982

Chemical circuitry and central cardiovascular regulation.

In attempting to sort out the functional components responsible for central cardiovascular regulation, circuits which can be defined by their neurotransmitter provide a focus for an initial simplified scheme. Three classes of transmitter-specific circuits can be developed from this perspective. The most prominent class, amino acid-mediated circuits, are illustrated by the presumptive excitatory glutamatergic excitatory efferent projections from baroreceptors to the nucleus tractus solitarius (NTS) and by presumptive inhibitory interneurons intrinsic to reticular system which use gamma-aminobutyrate as a transmitter. Secondly, monoamine-mediated intrinsic and extrinsic projections to the NTS are generally subsumed neuroanatomically within the so-called "non-specific" projection systems but recent cytochemical studies indicate that some organizational principles exist within NTS regions. A third class of chemically defined transmission consists of those circuits attributed to peptidergic neurons, such as endorphins, enkephalins, Substance P, or vasoactive-intestinal peptide (VIP). Although no classes of transmitters or transmitter mechanisms wholly unique to cardiovascular regulation have yet been identified, these 3 classes of transmitter can each mediate a broad range of integrative actions, through unique molecular mechanisms.

Amino Acids↗