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R P Hammer

Publications and source records attributed to R P Hammer.

At least 19 recordsLinked to original sources
PubMed1992

Effects of 1,3-di-o-tolylguanidine (DTG), a sigma ligand, on local cerebral glucose utilization in rat brain.

The 2-deoxy-D-[1-14C]glucose ([14C]DG) method was used to examine the effects of the relatively selective sigma ligand 1,3-di-o-tolylguanidine (DTG) on cerebral metabolism in freely moving rats. Each animal received an i.p. injection of DTG (0.2, 1, or 5 mg/kg) or normal saline 20 min prior to the infusion of [14C]DG. DTG induced dose-dependent changes in local cerebral glucose utilization (LCGU) in several motor and limbic structures. Most structures showed increases in LCGU, with a maximum effect at 1 mg/kg. The most profound increases in LCGU were observed in brain regions that are rich in sigma receptors. These included cerebellar and related nuclei (interpositus, lateral and medial cerebellar n., vestibular n., olivary n.), ambiguus n., superior colliculus (superior layers), hippocampus (CA2, CA3, DG), n. basalis of Meynert interpeduncular n., and the substantia nigra pars compacta and pars reticulata. No significant decreases in glucose utilization were observed at any dose. Although the areas affected by DTG are similar to those previously reported for other sigma ligands, future studies employing a range of doses for additional selective sigma ligands must be carried out in order to confirm whether these changes in LCGU were sigma-mediated.

Animals↗
PubMed1992

Parity-associated alterations of medial preoptic opiate receptors in female rats.

Preoptic area opiate receptor density was measured by quantitative autoradiography using [3H]naloxone in female rats during their first and second pregnancies and lactations and in a separate group of ovariectomized, nulliparous animals. Opiate receptor density in the medial preoptic area (MPOA) was elevated on day 12 of gestation in both primigravid and multigravid rats when compared with ovariectomized subjects. MPOA receptor density was reduced in primiparous mothers on day 5 of lactation relative to pregnancy. In contrast, receptor density in the MPOA did not decline in multiparous (second lactation) rats relative to pregnancy levels. Opiate receptor density was significantly higher on day 5 of lactation in multiparous than in primiparous mothers. No difference in receptor density was detected in the adjacent lateral preoptic area among the treatment groups. An examination of hormone titers revealed that basal prolactin levels were significantly higher in primigravid than multigravid rats, and that during lactation prolactin titers were negatively correlated with MPOA opiate receptor density in the primiparous mothers. The data demonstrate that multiple pregnancies and lactations result in changes of MPOA opiate receptor density and of circulating hormone levels. The findings are discussed in terms of the concurrent changes in neural opiate sensitivity associated with multiparity.

Analysis of Variance↗
PubMed1992

Domestication alters 5-HT1A receptor binding in rat brain.

Serotonin-1A receptor binding density was compared in the brains of wild and domesticated adult male Rattus norvegicus using in vitro receptor autoradiography of [3H]8-hydroxy-2-[n-dipropylamino]tetraline (DPAT). While both groups exhibited similar patterns of labeling, [3H]DPAT binding density was significantly (p less than or equal to 0.05) lower in the median raphe nucleus and greater in superficial entorhinal cortex and rostral dentate gyrus of domesticated compared to wild rats. The results suggest that specific serotonergic circuits from the median raphe nucleus to the entorhinal and hippocampal regions might be involved in regulation of the defensive behaviors that differ profoundly between wild and domesticated rats. The relationship of these putative differences to behavioral disorders such as anxiety and depression in humans is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Dynamic patterns of medial preoptic mu-opiate receptor regulation by gonadal steroid hormones.

The density of mu-opiate receptors located in the medial preoptic area (MPOA) of the rat hypothalamus is cyclical and sexually dimorphic. The hormonal regulation of MPOA mu-receptors was examined in ovariectomized rats treated with a variety of hormone regimens. In experiment 1, animals received acute estradiol (E2), progesterone (P), or prolactin (PRL), or E2 followed in 48 h by either P or vehicle by subcutaneous injection. Brains were removed 3 h after the final injection. In experiment 2, animals were implanted with empty or E2-filled Silastic capsules, and received either P or vehicle by injection 48 h later, at which time E2 capsules were removed. One group received E2 implants which remained in place following sham removal surgery. Brains and trunk blood for radioimmunoassay of E2 and P were collected 3, 27 or 51 h after the final injection. Frozen brain sections were prepared, incubated in [3H]D-Ala2,MePhe4,Gly-ol5-enkephalin, which selectively labels mu-receptors, and analyzed using quantitative receptor autoradiography. P treatment significantly increased MPOA mu-receptors, but only 27 h after E2 priming. Neither shorter P exposure, nor E2, P or PRL alone affected MPOA mu-receptor density. Following this delayed E2,P-induced increase, mu-receptor density subsequently decreased in the presence of absence of E2. The results suggest that E2,P treatment produces a gradual and transient increase of MPOA mu-receptor density. The subsequent decrease of receptor density is independent of the presence of E2 and may be related to receptor turnover. The time course of this effect is consistent with that of the estrus cycle. Such hormone-induced regulation of MPOA mu-receptor density could influence the physiologic effects of opiates on gonadotropin secretion and reproductive behavior in cycling females.

Animals↗
PubMed1992

Hormonal regulation of medial preoptic mu-opiate receptor density before and after parturition.

Endogenous opioid peptides acting in the medial preoptic area (MPOA) appear to be involved in the regulation of maternal behavior in lactating rats. Moreover, it is known that the density of mu-opiate receptors in the MPOA is elevated during pregnancy, but decreases during lactation. In the first experiment of this study, mu-receptor density in the preoptic area was examined across the periparturitional period on gestation days 18, 20 and 22, at 1 h postpartum and on postpartum days 1 and 12. The effect of pregnancy during lactation on mu-receptor density was also assessed. In addition, plasma hormone concentration of estradiol (E2), progesterone (P), and prolactin (PRL) were determined. While plasma P levels decreased and PRL levels increased prior to parturition, MPOA mu-receptor density remained elevated until 24 h after parturition before declining to reach a level similar to that of ovariectomized control animals. Receptor density was significantly correlated with PRL levels only in gestation day 22 animals, when PRL levels were highest. MPOA mu-receptor density was low at postpartum day 12 whether or not the animal was pregnant. No effects were observed in the adjacent lateral preoptic area in any group. In the second experiment, the effect of hormonal manipulation on preoptic opiate receptor density was examined at various times after removal of Silastic capsules containing P following sustained E2/P exposure. While P levels decreased abruptly following capsule removal, MPOA receptor density declined more gradually. The results are consistent with the hypothesis that a reduction of mu-receptor density occurs in the MPOA following parturition by receptor turnover in the absence of sufficient hormonal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Serotonin, but not dopamine, metabolites are increased in selected brain regions of subordinate male rats in a colony environment.

Subordinate male laboratory rats maintained in mixed-sex groups in a Visible Burrow System habitat show a complex pattern of stress-related changes including enhanced defensive behavior, early mortality and increased voluntary ethanol consumption. Analysis of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels indicated that 5-HT levels do not differ between colony subordinates, colony dominants, and singly-housed control animals. However, 5-HIAA levels were higher in subordinates than either dominants or control animals in the preoptic area, amygdala, hippocampus, and spinal cord, and, were higher than dominants only, in entorhinal cortex. Subordinates' regional 5-HIAA/5-HT ratios were reliably higher than those of dominant or control animals in midbrain and spinal cord and reliably higher than dominants only, in hypothalamus. Dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels and DA/DOPAC ratios were affected neither in hypothalamus nor midbrain. These findings suggest that a consistent increase of 5-HIAA levels in selected brain regions of subordinate rats may represent a biological substrate for a well-characterized pattern of alterations in defensive behaviors for these animals.

Animals↗
PubMed1991

Regional dependence of morphine-induced mu-opiate receptor down-regulation in perinatal rat brain.

The effect of perinatal morphine administration was examined in various brain regions using in vitro receptor autoradiography. Morphine was administered by continuous s.c. infusion of 10 mg/kg per day; brains of offspring were examined at five days of age. Morphine exposure reduced mu-receptor binding density in the preoptic area of hypothalamus, but not in the primary somatosensory cortex. mu-Receptor density was greater in the medial preoptic area of females than males, and in superficial layers of cortex in males than females. The results suggest that morphine has selective regional effects on mu-receptor ontogeny in rat brain.

Animals↗
PubMed1991

Delta 9-tetrahydrocannabinol alters cerebral metabolism in a biphasic, dose-dependent manner in rat brain.

delta 9-tetrahydrocannabinol (THC)-induced alterations in limbic and neocortical function are associated with deficiencies in short-term memory and recall. The 2-deoxy-D-glucose (2DG) autoradiographic method was used to examine the effect of acute THC administration (0, 0.2, 0.5, 2.0, 10.0 mg/kg) on regional brain metabolism in limbic and cortical brain regions of male rats. THC altered 2DG uptake in a biphasic, dose-dependent manner in most limbic and cortical structures, however most diencephalic and brainstem structures examined were unaffected. The 0.2 mg/kg THC dose significantly increased 2DG uptake relative to vehicle treatment in all cortical and selected limbic regions, whereas the 2.0 and 10.0 mg/kg THC doses decreased 2DG uptake in most of these regions. Certain limbic regions, particularly the hippocampus, are more sensitive to THC suggesting a selective regional action of the drug at lower doses. The incidence of enhanced metabolic activity in limbic and cortical regions is consistent with the occurrence of high density cannabinoid receptors in these regions.

Animals↗
PubMed1991

Gestational cocaine exposure increases opiate receptor binding in weanling offspring.

The use of cocaine during pregnancy produces a variety of adverse effects in offspring. Gestational cocaine exposure is known to affect developing dopamine systems, but other neurochemical systems may also be at risk. Regional density of opiate receptors labeled with [3H]naloxone was examined in the brains of 21-day-old male rats exposed to cocaine (0, 10, 20, or 40 mg/kg/day s.c.) between gestation days 8 and 20. Gestational cocaine exposure significantly increased labeling in a dose-dependent fashion in dopaminergic terminal (e.g. the nucleus accumbens, medial prefrontal cortex, olfactory tubercle, and caudatoputamen), limbic (e.g. basolateral amygdaloid nucleus, lateral habenula, hippocampus, dentate gyrus, entorhinal and cingulate cortices) and neocortical (e.g. somatosensory and motor cortices) regions, but had little effect in diencephalic or brainstem regions. The results suggest a functional linkage whereby drug-induced alteration of dopamine systems can regulate developing opioid systems in the brain. Moreover, gestational cocaine exposure produced long-lasting changes of opiate receptor labeling in certain brain regions. The implications of these results are uncertain. However, such effects on endogenous opioid systems could contribute to a developmental delay, cognitive or motor dysfunction.

Animals↗
PubMed1991

Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex.

The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative [14C]2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1991

Autoradiographic localization of dopamine D1 and D2 receptors in rat nucleus accumbens: resistance to differential rearing conditions.

The radioligands [3H]SCH 23390 and [3H]spiroperidol were used to label dopamine D1 and D2 receptors, respectively, in rat brain slices. Striatal sections were incubated in one of various concentrations of radioligand in the presence or absence of (+)-butaclamol and the resulting labeling was determined by liquid scintillation spectrometry. Scatchard analyses of the data revealed KD values of 1.18 nM for D1 receptors and 0.33 nM for D2 receptors. Tissue sections taken from the entire rostrocaudal extent of the nucleus accumbens, as well as other brain regions, were then processed for autoradiographic analysis of D1 and D2 receptors using a radioligand concentration equal to 1.5 X KD. After apposing the slices to 3H-sensitive film, topographical differences among brain areas were analysed using a quantitative densitometry system which determined the absolute amount of ligand binding relative to calibrated optical density standards. The nucleus accumbens exhibited a rostral-to-caudal density gradient for both D1 and D2 receptors. For D1 receptors, the density was similar across most of the nucleus accumbens, although the most caudal portion examined had a lower density than rostral portions. In contrast, the density of D2 receptors exhibited a more gradual gradient across the entire rostrocaudal extent of the nucleus accumbens. There was no significant rostrocaudal density gradient of either D1 or D2 receptors in either the olfactory tubercle or caudate-putamen in the same tissue sections. A lateral-to-medial gradient of D2 receptors was also present in the nucleus accumbens. That is, while there was no difference in the density of D1 receptors between the lateral core and medial shell subdivisions, the shell had a lower density of D2 receptors than did the core. The density of D1 and D2 receptors in the mesolimbic and nigrostriatal systems was compared in groups of animals raised from 30 to 60 days of age in an impoverished condition, a group-caged condition or an enriched condition. While the brain weight of enriched condition animals was higher than impoverished condition animals, there were no significant differences in the density of D1 or D2 receptors among the different groups. Apparently, the densities of D1 and D2 receptors in the brain are resistant to differential rearing conditions.

Animals↗
PubMed1991

Cyclization of disulfide-containing peptides in solid-phase synthesis.

Disulfide-containing peptides may be obtained in good yields and purities when oxidations are carried out on peptide chains anchored to polymeric supports used for solid-phase synthesis. Such approaches take advantage of the pseudo-dilution phenomenon which favors intramolecular processes. A variety of procedures have been demonstrated using the related model peptides Ac-Cys-Pro-D Val-Cys-NH2 and Ac-Pen-Pro-D Val-Cys-NH2 (which both readily assume a type II beta-turn conformation that becomes stabilized by a 14-membered disulfide-containing intramolecular ring), and oxytocin (conformationally mobile 20-membered disulfide ring). Both Boc and Fmoc were used for N alpha-amino protection, the beta-thiols of cysteine or penicillamine were blocked by S-acetamidomethyl (Acm), S-9-fluorenylmethyl (Fm), or S-trityl (Trt), and compatible anchoring linkages included HF-labile 4-methylbenzhydrylamide (MBHA), TFA-labile tris (alkoxy)benzylamide (PAL), and photolabile o-nitrobenzylamide (Nonb). Assemblies of linear sequences proceeded smoothly, and polymer-supported oxidations were carried out in a variety of ways either directly or after deblocking to the resin-bound dithiol. Chains were released from the support without substantial damage to the disulfide bridges, and overall yields were as high as 60-90%.

Amino Acid Sequence↗
PubMed1991

Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery.

2-[14C]deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine.

Analysis of Variance↗
PubMed1990

Perinatal opiate treatment delays growth of cortical dendrites.

Basilar dendritic arborizations of layer II-III pyramidal neurons in primary somatosensory cortex of 5-day-old male rats were reconstructed following perinatal morphine, morphine/naltrexone, or saline vehicle administration. Morphine treatment was observed to reduce total dendritic length. This effect was limited to higher order dendritic branches, with terminal dendrites manifesting the greatest reduction of length. The action of morphine was presumably mediated by opiate receptors, since concurrent naltrexone administration completely reversed morphine effects on dendritic length and branching. These results suggest that opiates act during late ontogenesis to affect dendritic growth in cerebral cortex.

Animals↗
PubMed1990

Mu-opiate receptor binding in the medial preoptic area is cyclical and sexually dimorphic.

The density and distribution of mu- and kappa-opiate receptors in the medial preoptic area (MPOA) of male and female rats across the estrous cycle was examined using quantitative in vitro autoradiography of [3H]D-Ala2,MePhe4,Gly-ol5-enkephalin (DAGO), [3H]naloxone and [3H]bremazocine binding. While no difference in kappa-receptor labeling was observed across sex or estrous stage, selective mu-receptor labeling with [3H]DAGO revealed a significant variation of density and distribution in the MPOA across the estrous cycle and between sexes. A dense concentration of mu-receptors located in the central, sexually dimorphic portion of the MPOA was observed during metestrus and diestrus in females, but not during proestrus nor in males. This region appeared to be the same as that labeled similarly using [3H]naloxone. These results suggest that a regional substrate for functional activation by endogenous opioid peptides (e.g. beta-endorphin) is cyclically regulated in females, which may explain the gonadal steroid-dependent effects of MPOA beta-endorphin on lordosis and luteinizing hormone secretion in females.

Animals↗
PubMed1990

Practical approach to solid-phase synthesis of C-terminal peptide amides under mild conditions based on a photolysable anchoring linkage.

Several 3-nitro-4-(N-protected aminomethyl)benzoic acids; with protection provided by tert.-butyloxycarbonyl (Boc), 9-fluorenylmethyloxycarbonyl (Fmoc), trifluoroacetyl (Tfa), dithiasuccinoyl (Dts), or phthaloyl (Phth), have been prepared by reproducible routes. Synthesis of Dts-handle 6 illustrates some particularly novel and efficient chemistry, and is preferred over more intricate routes to Boc-handle 3 and Fmoc-handle 4. The five handles were each evaluated for their application to the synthesis of peptide amides. Coupling onto amino-functionalized supports provided a general starting point for peptide chain assembly. The handle amino function was deblocked (Boc, Fmoc, Dts), the C-terminal residue was coupled as its N alpha-protected free acid, and ultimately the ortho-nitrobenzylamide anchorage linkage was cleaved photolytically to give the corresponding amide. Starting with handles 3, 4, and 6, several free and protected peptide amides were synthesized.

Amides↗
PubMed1989

Cocaine alters opiate receptor binding in critical brain reward regions.

Brain reward systems are thought to be involved in the reinforcing effect of both cocaine and opiates. In vitro receptor autoradiography was used to determine the effect of chronic, continuous cocaine exposure of 2 weeks duration on [3H]naloxone binding in various regions of rat brain. Although cocaine action in the central nervous system is usually associated with altered dopamine function, we observed that opiate receptor density as labeled by [3H]naloxone was altered by chronic cocaine exposure in critical brain reward regions, including the nucleus accumbens, ventral pallidum, and lateral hypothalamus. Endogenous opioid activity at opiate receptors in these critical regions may be associated with the reinforcement induced by both cocaine and opiates.

Animals↗