Biomedical subjects

R D Myers

Publications and source records attributed to R D Myers.

At least 37 records · Page 2Linked to original sources

PubMed1996

Suppression of alcohol preference in high alcohol drinking rats: efficacy of amperozide versus naltrexone.

The selectively bred high alcohol drinking (HAD) line of rat is considered as a potential model of one type of alcoholism. The purpose of the present experiments was to compare the efficacy of two drugs on the volitional drinking of the HAD rats: the 5-HT2A receptor antagonist, amperozide, and a nonselective antagonist of opiate receptors, naltrexone. To determine the pattern of alcohol drinking of the HAD rats, a standard preference test was used in which water was offered with alcohol increased in concentrations from 3% to 30% over 11 days. The maximally preferred concentration of alcohol of each rat was offered for 4 days and ranged from 7% to 20% with a mean intake of 6.9 g/kg per day. Initially, 1.0 mg/kg amperozide, 2.5 mg/kg naltrexone, or the saline vehicle were injected twice daily for 4 days at 1600 and 2200 hours. Secondly, 2.0 mg/kg amperozide, 5.0 mg/kg naltrexone, or the saline vehicle were administered also for 4 days. After the drug sequences, alcohol preference tests continued for another 4 days. Whereas the saline vehicle was without effect on drinking, the administration of either drug caused a significant dose-dependent reduction in the daily intake of alcohol by the HAD rats in terms of absolute g/kg and proportion of alcohol to water consumed. A comparison of the drinking response to the higher doses of the two drugs showed that amperozide was more efficacious in suppressing alcohol intake than naltrexone. Niether amperozide nor naltrexone exerted any significant effects on food and water intakes or on body weight. These results support the concept of a functional link in the brain between the serotonergic and opioidergic systems postulated to underlie, in part, the aberrant drinking of alcohol. A marked dissociation between the temporal patterns of drinking after naltrexone and amperozide treatment suggests that the opiate receptors mediate the immediate reinforcing effects of alcohol, whereas the more vegetative phenomena underlying addictive properties of alcohol are regulated by 5-HT2A receptors postsynaptic to serotonergic neurons. Finally, the inhibitory actions of both drugs imply that multiple receptor mechanisms within the mesolimbic and other systems in the brain underpin the addictive liability to alcohol.

Alcohol Deterrents↗

PubMed1996

Action of harman (1-methyl-beta-carboline) on the brain: body temperature and in vivo efflux of 5-HT from hippocampus of the rat.

Harman (1-methyl-beta-carboline) has been shown previously to act on the hippocampus of the rat in terms of its evocation of anxiogenic responses and induction of alcohol preference. In the present experiments, the localized perfusion of 200 microM harman in the dorsal hippocampus of freely moving rats increased the levels of serotonin (5-HT) but not 5-hydroxyindoleacetic acid (5-HIAA) in cerebral dialysates. The systemic administration of 5.0-20 mg/kg harman also enhanced 5-HT in the perfusates but reduced the levels of 5-HIAA in a dose-dependent manner, probably as a result of the inhibition of the enzyme monoamine oxidase type A (MAO-A). Harman given systemically in doses of 2.5-20 mg/kg induced an intense hypothermia, with a maximum fall produced by the 5.0 mg/kg dose. This fall in body temperature (Tb) induced by 5.0 mg/kg harman was not antagonized by 5.0 mg/kg of (+/-)-pindolol. Further, pretreatment of the rats with parachlorophenylalanine (pCPA) also failed to alter the harman-induced hypothermia. The systemic administration of 10 mg/kg of the MAO-A inhibitor, clorgyline, also lowered Tb significantly. Overall, the present experiments show that harman apparently influences 5-HT systems in the brain by its action in inhibiting MAO-A. This property is likely responsible also for the harman-induced increase of 5-HT in the hippocampus of the rats.

Adrenergic beta-Antagonists↗

PubMed1996

Tetrahydroisoquinolines and alcoholism: where are we today?

The present status of research on the tetrahydroisoquinoline (THIQ) family of compounds and other aldehyde metabolites in the field of alcoholism is described. A brief history of the background of experimental studies on the actions of the THIQ's and beta-carbolines on alcohol drinking is presented. A computer data base search of articles published in this field reveals that both the historical and current research trends have waxed and waned since the 1960s. The clinical utility of naltrexone in terms of the cerebral function of opioid compounds in drinking behavior and alcoholism is likewise considered. Finally, the residual controversy concerning the significance of multiple intermediary metabolites in alcohol dependence and craving should ultimately be resolved in the future by broad-based investigations which employ state-of-the-art experimental approaches.

Alcoholism↗

PubMed1995

Fever induced in rats by intrahypothalamic macrophage inflammatory protein (MIP)-1 beta: role of protein synthesis.

The effect of macrophage inflammatory protein-1 beta (MIP-1 beta) on body temperature, following its injection into the anterior hypothalamic pre-optic area (AH/POA), was examined by a radiotelemetry system in the freely moving rat. The purpose of this study was to examine the action of an inhibitor of protein synthesis, anisomycin, on the pyrexia which follows intrahypothalamic injection of MIP-1 beta. The micro-injection of 10 to 20 pg MIP-1 beta into the AH/POA induced a dose-dependent monophasic increase in body temperature, whereas a higher dose of 25 pg of the cytokine caused a biphasic febrile response. When MIP-1 beta was heated at 70 degrees C for 30 min prior to its administration, the pyrogenic response was abolished. Pretreatment of the micro-injection site in the AH/POA with 10 micrograms anisomycin did not alter the febrile response to 25 pg MIP-1 beta given at the same site in the AH/POA. When 10 mg/kg anisomycin was administered subcutaneously, the febrile response to 25 pg MIP-1 beta injected in the AH/POA was significantly suppressed. The present results suggest that fever caused by MIP-1 beta within the cells of the AH/POA may not require the synthesis of a new protein factor; however, the de novo synthesis of a protein outside of the AH/POA presumably plays a functional role, at least in part, in the intense fever produced by this cytokine in the hypothalamus.

Animals↗

PubMed1995

Selective destruction of midbrain raphe nuclei by 5,7-DHT: is brain 5-HT involved in alcohol drinking in Sprague-Dawley rats?

Since serotonin (5-HT) reportedly is involved in aberrant drinking of ethyl alcohol, the present study examined a possible role of the concentration of 5-HT in systems originating in the dorsal raphe nucleus (DRN), median raphe nucleus (MRN) or both nuclei. The preference for alcohol offered in concentrations increased over 10 days from 3% to 30% was determined for each Sprague-Dawley rat. After the rats were anesthetized with sodium pentobarbital, either 10 microg 5,7-DHT or artificial cerebrospinal fluid (CSF) was micro-injected stereotaxically into the DRN, MRN or both nuclei. After 10 days, a second alcohol preference test was offered to the animals. Then the rats were decapitated, each brain removed, and the block of tissue containing injection sites was saved for histological analysis. The remaining portion was dissected into separate regions for analysis by HPLC of 5-HT, 5-hydroxyindoleacetic-acid (5-HIAA), norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The 5,7-DHT lesion of the DRN depleted the levels of 5-HT and 5-HIAA by 50-55% in the midbrain and pons and by 70-80% in the frontal cortex, whereas, the 5,7-DHT lesion of MRN reduced 5-HT in all regions except the corpus striatum. The depletion of 5-HT was lower in MRN-lesioned than in DRN-lesioned rats in the frontal cortex and nucleus accumbens. The combined lesion of both DRN and MRN produced a massive decline of >90% of 5-HT and 5-HIAA in all structures except the pons where 5-HT was reduced by 70%. Whereas the level of NE was reduced mainly in the frontal cortex, the levels of DA and its metabolites were essentially unaffected by the 5,7-DHT lesions. Although single or combined lesions of the DRN and MRN failed to alter the intake of alcohol of the rats, the combined serotonergic lesions increased significantly the ingestion of water but not food. Correlational analyses in the sham groups showed a negative association between the intake of alcohol and cortical dopamine and possible hippocampal 5-HT and NE as well as between the ingestion of food and of 5-HT in the frontal cortex. Taken together, these observations in the Sprague-Dawley rat suggest that lower levels of these monoamines in certain regions of the brain may play a role in the maintenance of the basal intake of alcohol but not in the drinking after the injection of 5,7-DHT. Explanations of our findings include: (1) a compensatory neurochemical change in pre- or postsynaptic 5-HT receptors subsequent to the dysfunction of serotonergic neurons in the forebrain; (2) a unique characteristic of the Sprague-Dawley strain of rat; and (3) residual quanta of 5-HT which sustains the pattern of alcohol drinking.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

5-HT, dopamine, norepinephrine, and related metabolites in brain of low alcohol drinking (LAD) rats shift after chronic intra-hippocampal infusion of harman.

Harman (1-methyl-beta-carboline) has been shown to induce preference for alcohol in the genetically bred, low alcohol drinking (LAD) rat. This study was undertaken in the LAD rat to determine whether monoamines and their metabolites in different regions of the brain are altered by harman infused chronically into the dorsal hippocampus. For this purpose, a cannula was implanted stereotaxically into the dorsal hippocampus. The cannula was attached to an osmotic minipump implanted subcutaneously within the intrascapular space. The pump was filled with either an artificial cerebrospinal fluid (CSF) vehicle or harman, which was delivered at a rate of 1.0 or 3.0 micrograms/h (i.e., 5.5 or 16.5 nmol/h, respectively) for a period of 14 days. Four days after surgery, a standard preference test for ethyl alcohol was given to the rats over 10 days in which concentrations were increased daily from 3%-30%. The higher concentration of harman infused into the hippocampus elevated the level of serotonin (5-HT), both ipsilateral and contralateral to the hippocampal site of infusion, as well as in the midbrain, frontal cortex, striatum and nucleus accumbens. Similarly, this treatment resulted in a rise in the levels of norepinephrine in the hippocampus and midbrain but decreases in dopamine levels in the pons. The levels of 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were diminished in the pons of rats given 3.0 micrograms/h harman, whereas both concentrations of the beta-carboline reduced the level of homovanillic acid (HVA) in the frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Tomato juice, chocolate drink, and other fluids suppress volitional drinking of alcohol in the female Syrian golden hamster.

Although the hamster generally prefers alcohol at a level similar to that of the rat or mouse selectively bred to consume alcohol, the drinking hamster demonstrates neither physical dependence on alcohol nor elevated blood levels of alcohol, which are two typical criteria characterizing an animal model of alcoholism. The present investigation was designed to determine whether a third criterion of an animal model (i.e., consumption of high levels of alcohol in the presence of a palatable fluid, fulfilled by the P rat) would be met by the female Syrian golden hamster (Mesocricetus auratus). A standard 3-bottle preference test was undertaken in 6 female hamsters over an 11 day period, in which water was presented in one tube and, in a second tube, a v/v solution of alcohol which was increased in concentration from 3% to 50% on each day as follows: 3%, 5%, 7%, 9%, 12%, 15%, 20%, 25%, 30%, 40%, and 50%. Then each hamster was offered its individually determined, maximally preferred concentration of alcohol for 4-8 days, which was 20%, 25%, or 30% alcohol. The mean absolute intake of alcohol during this period was 17.9 +/- 1.1 g/kg per day, whereas the mean proportion of alcohol to total fluid was 0.68 +/- 0.05. Then over a 4-day interval, a solution of tomato juice, peach juice, mango juice, dextrose and a chocolate beverage (Ensure Plus), all made isocaloric to the alcohol solutions with dextrose, was placed in the third tube simultaneously with water and the individually preferred concentration of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

PubMed1995

Cytokines and thermoregulation: interleukin-9 injected in preoptic area fails to evoke fever in rats.

A number of the members of the family of cytokines including IL-1, IL-2, IL-6, and IL-11 act directly in the brain to induce a febrile response in the rat and other species. The purpose of this study was to examine the effect of interleukin-9 (IL-9) when this cytokine is applied directly to the thermosensitive and pyrogen reactive region of the anterior hypothalamic, preoptic area (AH/POA). In male Sprague-Dawley rats, guide cannulae for microinjection into the AH/POA were implanted stereotaxically, and radio transmitters for monitoring body temperature (Tb) were placed intraperitoneally. Following postoperative recovery, recombinant murine macrophage inflammatory protein (MIP)-1 beta was microinjected in the AH/POA of each rat in a dose of 28 pg/microliters to identify pyrogen reactive sites in the AH/POA. Then recombinant human IL-9 was suspended in pyrogen-free CSF vehicle and microinjected in the same sites in concentrations of 2.4, 24, and 240 U/microliters. In contrast to the pyrexic action of MIP-1 beta, IL-9 failed to elicit a significant alteration in the Tb of the rats at any of the doses tested. IL-9 was also without effect on the intakes of either water or food. These results demonstrate that IL-9 applied to the region of the diencephalon in which other cytokines act to evoke fever may not play a direct role in the thermogenic component underlying the acute phase response. However, as demonstrated in several different cell systems, IL-9 may require a cofactor related to pyrogen for a febrile response to develop.

Animals↗

PubMed1995

Anorexic action of a new potential neuropeptide Y antagonist [D-Tyr27,36, D-Thr32]-NPY (27-36) infused into the hypothalamus of the rat.

Neuropeptide Y (NPY) produces a vigorous feeding response in several species when it is injected into hypothalamic structures involved in eating behavior. The purpose of this study was to determine whether a unique carboxy terminal fragment of NPY would alter the pattern of eating induced in the rat either by NPY injected into the hypothalamus or by a 24-h period of food deprivation. In this case, two L-tyrosine residues and one L-threonine residue of the NPY27-36 fragment were transformed to their D-conformation to produce [D-Tyr27,36,D-Thr32]-NPY (27-36), i.e., D-NPY27-36. Guide cannulae for microinjection were implanted stereotaxically just dorsal to the paraventricular nucleus (PVN) or ventromedial hypothalamus (VMH) of 24 adult male Sprague-Dawley rats. Following postoperative recovery, a microinjection of artificial CSF or 1.1 microgram or 3.3 micrograms of a peptide was made directly into the PVN or VMH as follows: native NPY; D-NPY27-36; or [L-Tyr27,36, L-Thr32]-NPY (27-36), i.e., L-NPY27-36. Food intakes were measured at intervals of 0.25, 0.5, 1.1, 2.0, 4.0, and 24 h. When D-NPY27-36 was microinjected at NPY reactive sites in the PVN or VMH of the rat 15 min before a similar microinjection of NPY, the intense eating response induced by the peptide was reduced significantly. Not only was the effect dose dependent, but D-NPY27-36 also augmented the latency to feed. A mixture of the two doses of NPY and D-NPY27-36 injected at the same hypothalamic loci did not attenuate the intake of food but tended to enhance the feeding response in the rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Synthesis of dopamine and 5-HT in anatomical regions of the rat's brain is unaffected by sustained infusion of amperozide.

The 5-HT2A antagonist, amperozide, is considered to be a potentially useful drug for the treatment of substance abuse. The effects of this drug on the Sprague-Dawley rat were examined on the synthesis of dopamine and serotonin (5-HT) as well as on the intakes of food and water and the level of body weight. Amperozide was delivered subcutaneously by osmotic minipump in doses of 2.5 mg/kg or 5.0 mg/kg per day for 7 days. After injection of 100 mg/kg NSD-1015, each brain was dissected post mortem into midbrain, pons, hypothalamus, septum, nucleus accumbens, striatum, frontal cortex and the hippocampus. Neither concentration of amperozide altered the synthesis of dopamine or 5-HT, as measured in terms of the formation of 1-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP), respectively, in any of the 8 brain regions analyzed. Both doses of amperozide reduced food intake by 20% within 24 hr after implantation of the pumps, but feeding resumed postoperatively at the control level within 48 hr. Amperozide affected neither the intake of water nor the level of body weight. The lack of effect on the synthesis of dopamine and 5-HT and the absence of side effects on the intakes of food and water suggest that amperozide may be a specific agent for suppressing alcohol drinking.

Alcoholism↗

PubMed1994

Fever and feeding in the rat: actions of intrahypothalamic interleukin-6 compared to macrophage inflammatory protein-1 beta (MIP-1 beta).

The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1 beta, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre-optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (Tb) of MIP-1 beta with that of interleukin-6 (IL-6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro-injections, radio transmitters which monitor Tb continuously were inserted intraperitoneally in each of 15 male Sprague-Dawley rats. Each micro-injection was made in a site in the AH/POA in a volume of 1.0 microliter of pyrogen-free artificial CSF, recombinant murine MIP-1 beta, or recombinant human IL-6. MIP-1 beta in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in Tb of 2.4 +/- 0.21 degrees C reached by 3.7 +/- 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL-6 induced a dose dependent fever of similar latency and a mean maximal increase in Tb of 1.2 +/- 0.25 degrees C, 1.8 +/- 0.15 degrees C, and 2.1 +/- 0.22 degrees C and duration of 6.2 +/- 1.28 hr, 6.7 +/- 0.49 hr, and 6.8 +/- 0.65 hr when given in doses of 25, 50, and 100 ng, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Chemokine-induced fever: intracerebroventricular actions of MIP-1 and MIP-1 alpha in rats.

The central pyrogenic actions in the rat of doublet macrophage inflammatory protein-1 (MIP-1) and MIP-1 alpha were determined by their intracerebroventricular infusion. Doses of 560 pg and 11.2 ng of MIP-1 or 10.0 ng MIP-1 alpha infused into the third cerebral ventricle induced a long lasting fever. However, MIP-1 alpha was much less potent than MIP-1 in terms of intensity and longer latency. Overall, these cytokines are pyrogenic when acting on the walls of the third ventricle; however, a dose 10 times greater than that injected directly into the anterior hypothalamus is required to evoke fever, as based on earlier experiments. Finally, circulating MIP-1 could act centrally by its entry through the choroid plexus into the ventricular system of the brain.

Animals↗

PubMed1994

Fever of unknown origin: due to C. albicans or other fungi acting on the hypothalamus?

Recently, it was shown that cerebrospinal fluid (CSF) contaminated with the fungus Trichosporon beigelii produces an intense fever when the organism is microinjected directly into the thermosensitive region of the anterior hypothalamic preoptic area (AH/POA). The purpose of this study was to determine if the AH/POA possesses a corresponding sensitivity to another fungal organism, Candida albicans. In adult male Sprague-Dawley rats, an intracerebral cannula was implanted stereotaxically above the AH/POA and a radio transmitter for the continuous recording of body temperature (Tb) was placed in the peritoneal cavity. After recovery, one of two solutions was microinjected in the AH/POA: a pyrogen-free, filtered artificial CSF and a second cultured with C. albicans in a concentration of approximately 12 x 10(8) organisms/ml. Whereas the filtered CSF failed to evoke a significant rise in Tb, C. albicans produced a febrile response of 0.8-1.5 degrees C in the rats within 1 h after its microinjection into the AH/POA. This fever persisted typically for > or = 12 h but after 24 h Tb returned to the baseline. Histological examination of the cerebral tissue postmortem revealed focally extensive granulomatous encephalitis with disseminated inflammation throughout the parenchyma of rats given repeated microinjections of C. albicans. Since C. albicans is a highly potent pyrogen acting directly on thermosensitive neurons, it is envisaged that a massive accumulation of the organism within the brain could be responsible pathologically for the protracted fever "of unknown origin" which gives rise to clinical morbidity.

Animals↗

PubMed1994

Fever produced by interleukin-11 (IL-11) injected into the anterior hypothalamic pre-optic area of the rat is antagonized by indomethacin.

A number of cytokines including the family of interleukins and the macrophage inflammatory proteins act in the brain to produce fever. The purpose of this study was to determine whether the recently discovered hematopoietic progenitor cell stimulator, interleukin-11 (IL-11), alters the body temperature (Tb) of the rat when the cytokine is delivered directly to the thermosensitive and pyrogen reactive region of the hypothalamus. A guide cannula for micro-injection into the anterior hypothalamic pre-optic area (AH/POA) was implanted stereotaxically in each of 19 male Sprague-Dawley rats. A Mini-mitter transmitter for continuous monitoring of Tb of the animal was implanted i.p. Following postoperative recovery, recombinant human IL-11 was micro-injected in a volume of 1.0 microliter into the AH/POA in a dose of 2.7, 13.5, 27 or 250 ng. rhuIL-11 evoked a dose dependent fever with a mean rise in Tb of 0.91 +/- 0.06 degrees C, 1.68 +/- 0.11 degrees C and 0.99 +/- 0.08 degrees C following 13.5 ng, 27 ng and 250 ng, respectively. No significant change in Tb of the rats was produced by 2.7 ng IL-11 or the CSF control vehicle. A significant decline in the intake of food occurred also after the micro-injection of the 27 ng of IL-11. Prior treatment of the rat with 5.0 mg/kg of a prostaglandin synthesis inhibitor, indomethacin, administered intraperitoneally attenuated significantly the febrile response induced by the 250 ng dose of IL-11. These results demonstrate that IL-11 possesses potent thermogenic properties when acting within the ventral forebrain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Increased alcohol intake in low alcohol drinking rats after chronic infusion of the beta-carboline harman into the hippocampus.

Harman (1-methyl-beta-carboline) has been shown to induce volitional drinking of ethyl alcohol in the rat. The purpose of this study was to examine the long-term effect of sustained delivery of harman into the dorsal hippocampus on the subsequent preference for alcohol in the genetically bred low alcohol drinking (LAD) rat. The individual pattern of preference for alcohol was first determined following a standard 3-30% alcohol self-selection test for 10 days. Thereafter, a cerebral cannula for constant infusion was implanted stereotaxically into the dorsal hippocampus. The cannula was attached to an osmotic minipump implanted subcutaneously, which was filled with either an artificial cerebrospinal fluid (CSF) vehicle or harman. Harman was delivered at a rate of 1.0 or 3.0 micrograms/h (i.e., 5.5 or 16.5 nmol/h, respectively) for a period of 14 days. Four days after surgery, the rats underwent a second 3-30% alcohol preference test for 10 days. Both doses of harman induced a threefold increase in the voluntary consumption of alcohol, expressed as g/kg per day. This effect of the beta-carboline seems to be specific for ethanol because its intake by the LAD rats was increased significantly only when concentrations from 11% to 30% were presented. Harman also enhanced the daily intake of food in a dose-dependent manner, but did not affect body weights or the volumes of water and total fluid consumed. These results, thus, demonstrate that the long-term exposure of hippocampal neurons to harman induces a preference for high concentrations of alcohol even in a line of rats lacking such a genetic predisposition.

Alcohol Drinking↗

PubMed1994

Genetics of alcoholism: simultaneous presentation of a chocolate drink diminishes alcohol preference in high drinking HAD rats.

Through selective crossbreeding of the N/Nih heterogeneous stock of rats, two genetic lines of rats have been developed that are categorized by their preference for ethyl alcohol as high alcohol drinking (HAD) and low alcohol drinking (LAD) animals. Corresponding to other strains of rat bred for alcohol selection or rejection, they were subdivided on the basis of their intake of a solution of 10% alcohol vs. water. The present experiments were designed to determine whether the HAD-1 and LAD-1 lines are similar to the P and NP rats in their profile of alcohol consumption. Five successive three-bottle preference tests for alcohol drinking in the presence of water were undertaken in both HAD (n = 9) and LAD (n = 10) rats as follows: 10% alcohol for 5 days; 3-30% concentrations of alcohol increased over 11 days; the maximally preferred concentration of alcohol for 5 days; this maximally preferred concentration of alcohol plus either chocolate Slender for 5 days, or an aspartame solution for 5 days. The intake of alcohol of the LAD rats during the 10% test was 0.4 g/kg/day, whereas during the 3-30% test, the maximum intake was 1.7 g/kg/day; their maximally preferred concentrations ranged between 7% and 9% alcohol. In contrast, the intake of 10% alcohol of the HAD rats was 6.5 g/kg/day, whereas during the 3-30% test the mean daily intake was 6.6 g/kg/day; the maximally preferred solutions of the HAD rats ranged between 13 to 20%, with the mean maximum intake of 10.57 g/kg/day reached at the 20% concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

PubMed1994

Prostaglandins and hypothalamic neurotransmitter receptors involved in hyperthermia: a critical evaluation.

The role of a prostaglandin of the E series (PGE) in the hypothalamic mechanisms underlying a fever continues to be controversial. This paper reviews the historical literature and current findings on the central action of the PGEs on body temperature (Tb). New experiments were undertaken to examine the local effect of muscarinic, nicotinic, serotonergic, alpha-adrenergic, or beta-adrenergic receptor antagonists at hypothalamic sites where PGE1 caused a rise in Tb of the primate. Guide tubes for microinjection were implanted stereotaxically above sites in and around the anterior hypothalamic, preoptic area (AH/POA) of male Macaque monkeys. Following postoperative recovery, 30-100 ng of PGE1 was micro-injected unilaterally in a volume of 1.0-1.5 microliter at sites in the AH/POA to evoke a rise in Tb, and once identified, pretreated with a receptor antagonist. PGE1 hyperthermia was significantly reduced by microinjections of the muscarinic and nicotinic antagonists, atropine, or mecamylamine, at PGE1 reactive sites in the AH/POA. The serotonergic antagonist, methysergide, injected at PGE1 sensitive sites in the ventromedial hypothalamus also attenuated the rise in Tb. However, the 5-HT reuptake blocker, fluoxetine, and the beta-adrenergic receptor antagonist, propranolol, injected in the AH/POA failed to alter the PGE1 hyperthermia. In contrast, the alpha-adrenergic antagonist, phentolamine, potentiated the increase in Tb at all PGE1 reactive sites in the hypothalamus. An updated model is presented to explain how the concurrent actions of aminergic neurotransmitters acting on their respective receptors in the hypothalamus can interact with a PGE to elicit hyperthermia. Finally, an evaluation of the current literature including recent findings on macrophage inflammatory protein (MIP-1) supports the conclusion that a PGE in the brain is neither an obligatory nor essential factor for the expression of a pyrogen fever.

Adrenergic alpha-Antagonists↗

PubMed1994

Neuroactive peptides: unique phases in research on mammalian brain over three decades.

Because of the enormous growth over the last three decades of research on the role of peptides in the brain, the need became apparent to determine the status of these compounds in terms of their current research interest. Since 1965, over a quarter of a million research papers have been published on peptides that have since been classified as neuroactive. The present study was undertaken to analyze systematically the yearly trends of research emphasis in neuroactive peptides as reflected by their individual frequency of publication by year, beginning in 1966. A computer analysis of the publication characteristics was carried out using the Medline data base in which the citation search was limited to the topic brain crossed with the topic mammal. One criterion for the inclusion of a given peptide in the analysis was a frequency of 25 or more citations following its discovery, as related to the mammalian brain. The 42 peptides that met this criterion were: adrenocorticotropic hormone, angiotensin II, atrial natriuretic factor, bombesin, bradykinin, calcitonin, calcitonin gene-related peptide, carnosine, beta-casomorphin, cholecystokinin, corticotropin-releasing factor, delta sleep-inducing peptide, dynorphin, beta-endorphin, Leu-enkephalin, Met-enkephalin, galanin, gastrin, glucagon, growth hormone, growth hormone-releasing factor, insulin, kyotorphin, beta-lipotropin, luteinizing hormone-releasing factor, melanocyte-stimulating hormone release inhibitory factor-1, alpha-melanocyte-stimulating hormone, motilin, neurokinin A, neurokinin B, neuropeptide Y, neurotensin, oxytocin, pituitary adenylate cyclase activating polypeptide, peptide HI, prolactin, secretin, somatostatin, substance P, thyroid-releasing hormone, vasopressin, and vasoactive intestinal peptide. An overall analysis of the 298,105 papers published on these 42 peptides since 1965 revealed that the research activity of 24,742, or 8.30%, of the studies, focused on their neuroactive properties. Taken as a whole, the research on neuroactive peptides reached a peak in 1986, as reflected by the total of 1793 papers published during that year. Although the level of publication has fluctuated between 1548 and 1774 research papers over the last 6 years, it is now clear that the trend in research on neuroactive peptides has reached an asymptote today that shows no sign of deviation. A temporal analysis year by year of individual publication profiles revealed three distinct trends: 1) peptides showed a slow development in research interest and did not exceed more than 15-30 publications per year; 2) peptides exhibited a steady increase in research activity over the years that continues today; and 3) peptides displayed an initial, often intense, research emphasis that inexplicably declined, in some cases precipitously, in the mid 1980s.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗