Biomedical subjects

Fred Nyberg

Publications and source records attributed to Fred Nyberg.

47 records · Page 3Linked to original sources

PubMed2003

"Binge" cocaine differentially alters preproenkephalin mRNA levels in guinea pig brain.

Male Hartley guinea pigs were administered i.p. injections of cocaine or saline for 2 or 7 days in a "binge" paradigm. RNA was isolated from dissected brain regions and levels of preproenkephalin mRNA and total RNA were quantified by RNase protection assays. Following 2 days of "binge" cocaine administration, no significant alterations in preproenkephalin mRNA levels were detected in six brain regions. Following 7 days of cocaine administration, however, lower levels of preproenkephalin mRNA were observed in the nucleus accumbens and hypothalamus of cocaine-treated animals and higher levels in the frontal cortex and amygdala. These findings differed from previous studies in the rat, so an additional experiment was performed with animals treated at the 7 day time point. For increased statistical power, data from the two experiments were combined and examined by two-way ANOVAs; in this combined analysis, increases in preproenkephalin mRNA were observed in frontal cortex, amygdala, and hippocampus, decreases were found in the nucleus accumbens and hypothalamus, with no change in thalamus, caudate putamen, or cerebellum. These observed differences between guinea pigs and rats make this species an interesting model for neurobiological studies of cocaine-induced alterations in neuropeptide gene expression in the mammalian brain.

Animals↗

PubMed2003

In vivo processing of LVV-hemorphin-7 in rat brain and blood utilizing microdialysis combined with electrospray mass spectrometry.

In vivo microdialysis in combination with liquid chromatography/electrospray time-of-flight mass spectrometry was used to study the processing of LVV-hemorphin-7, an endogenous decapeptide with opioid activity, in rat brain and blood. A microdialysis probe (flow rate 0.4 microL/min) was used to both introduce LVV-hemorphin-7 into the striatum of the brain (1.0 pmol/microL) or the venous blood (10 pmol/microL) and to collect the metabolic products. LVV-hemorphin-7 was extracellularly metabolized in the striatum to form C-terminal fragments 2-10, 3-10, 4-10, 5-10, 6-10, 7-10, and N-terminal fragments 1-9, 1-8, 1-6. Infusion of the aminopeptidase inhibitor amastatin (1.0 pmol/microL) into the striatum, together with LVV-hemorphin-7, decreased the processing of LVV-hemorphin-7 to form C-terminal fragments 2-10, 3-10, 4-10, but increased the relative levels of fragment 5-10 and N-terminal fragments 1-9, 1-8 and 1-6. The major metabolic product from LVV-hemorphin-7 in the striatum was the C-terminal fragment 5-10, which may be processed by an endopeptidase not sensitive to amastatin. The LVV-hemorphin-7 infusion to the venous blood produced the C-terminal fragments 2-10, 3-10, 4-10, and 5-10, N-terminal fragment 1-9, and internal fragments 4-7 and 4-9. It is concluded that the combination of microdialysis and electrospray mass spectrometry provides a powerful tool for the study of extracellular metabolism and kinetic processes of complex reaction systems in vivo.

Animals↗

PubMed2003

Substance P(1-7) affects the expression of dopamine D2 receptor mRNA in male rat brain during morphine withdrawal.

Previous studies have confirmed an important role of the undecapeptide substance P (SP) in opioid reward and dependence. It is further shown that the SP N-terminal metabolite SP(1-7) may attenuate the intensity of opioid withdrawal in mice. In this study we have investigated the effect of the heptapeptide fragment on the expression of the brain dopamine D2 receptor mRNA and on the withdrawal reaction, as well, in morphine-dependent rats. Male Sprague-Dawley rats were randomly distributed into two groups. Guide cannula was implanted and aimed at the lateral ventricle and animals were subsequently made opioid dependent by two daily injections of morphine (10 mg/kg) for 7 days. Half an hour before naloxone challenge (2 mg/kg) one group of rats received an injection of SP(1-7) (28 nmol per rat) and the other, serving as control, was injected with saline through the cannula. Animals were decapitated 4 h following SP(1-7) or saline injections. The results indicated that the level of the dopamine D2 receptor transcript was significantly reduced by SP(1-7) in nucleus accumbens and frontal cortex but not altered in the striatum. In behavioral tests it was found that the heptapeptide attenuated several somatic withdrawal symptoms. The observed reduction in the receptor transcript in nucleus accumbens and frontal cortex is suggested to reflect an increased dopamine activity in these areas, which in turn may counteract the withdrawal reaction.

Animals↗

PubMed2002

Anabolic androgenic steroid affects competitive behaviour, behavioural response to ethanol and brain serotonin levels.

The present study investigated whether anabolic androgenic steroid (AAS) treatment (daily subcutaneous injections during 2 weeks with nandrolone decanoate; 15 mg/kg) affects competitive behaviour, and locomotor activity response to a sedative dose of ethanol (0.5 g ethanol/kg). In addition, levels of brain monoamines were assessed. The results showed that AAS treated animals exhibited enhanced dominant behaviour in the competition test compared to controls. The AAS groups' locomotor activity was not affected by ethanol in contrast to the controls who showed a sedative locomotor activity. AAS animals had significant lower levels of serotonin in basal forebrain and dorsal striatum compared to controls. These findings further strengthen the fact that AAS affects behaviour, as well as biochemical parameters. Based on previous studies and results from the present study, we hypothesize that AAS abuse may constitute a risk factor for disinhibitory behaviour, partly by affecting the serotonergic system.

Anabolic Agents↗

PubMed2002

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N-methyl-D-aspartate receptor subunits gene transcripts in male rats.

Studies were conducted to evaluate the effects of s.c. injected recombinant human growth hormone (GH) on the expression of the gene transcript of N-methyl-D-aspartate receptor subunits type 1 (NR1), type 2A (NR2A), and type 2B (NR2B) in the male rat hippocampus. The GH-induced effects on the expression of hippocampal gene transcripts of GH receptor (GHR) and GH-binding protein were also examined. Male Sprague-Dawley rats, kept in four groups of two different ages, was treated with the hormone or saline during 10 days before decapitation and tissue dissection. Brain tissues collected were analyzed for mRNA content by using the Northern blot technique. The results indicated that in adult young rats (11 weeks of age) the hormone elicited a decrease in the mRNA expression of NR1 but an increase in that of the NR2B subunit. In elderly adult rats (57-67 weeks of age) GH induced an increase in the expression of the hippocampal message for NR1 and NR2A. Meanwhile, the hormone induced a significant up-regulation of the GHR transcript in hippocampus of adult young rats but not in elderly adult rats. It was further found that a significant positive correlation exists between the level of GHR mRNA and the expression of the NR2B subunit transcript in adult young rats. The GH-induced increase in the expression of hippocampal mRNA for the NR2B subunit is compatible with a previously observed memory promoting effect seen for the hormone, because overexpression of this N-methyl-D-aspartate receptor subunit is shown to enhance cognitive capabilities.

Aging↗

PubMed2002

Vinyl sulfide cyclized analogues of angiotensin II with high affinity and full agonist activity at the AT(1) receptor.

Vinyl sulfide cyclized analogues of the octapeptide angiotensin II that are structurally related to the cyclic disulfide agonist c[Hcy(3,5)]Ang II have been prepared. The synthesis relies on the reaction of the mercapto group of a cysteine residue in position 3 with the formyl group of allysine incorporated in position 5 of angiotensin II. A mixture of the cis and the trans isomers was formed, and these were separated and isolated by RP-HPLC. Thus, the three-atom CH(2)[bond]S[bond]S element of the AT(1) receptor agonist c[Hcy(3,5)]Ang II has been displaced by a bioisosteric three-atom S[bond]CH[double bond]CH element. A comparative conformational analysis of the 13-membered ring systems of c[Hcy(3,5)]Ang II and the 13-membered cyclic vinyl sulfides with cis and trans configuration, respectively, suggested that all three systems adopted very similar low-energy conformations. This similarity was also reflected in the bioactivity. Both of the compounds that contained the ring systems encompassing the cis or trans vinyl sulfide elements between positions 3 and 5 exhibited K(i) values less than 2 nM and exerted full agonism at the AT(1) receptor. In contrast, vinyl sulfide cyclization involving the amino acid residues 5 and 7 rendered inactive compounds. The cyclic vinyl sulfides that have agonist activity were both shown to possess low-energy conformers compatible with the previously proposed 3D model for the bioactive conformation of Ang II.

Angiotensin II↗

PubMed2002

Injection of substance P (SP) N-terminal fragment SP(1-7) into the ventral tegmental area modulates the levels of nucleus accumbens dopamine and dihydroxyphenylacetic acid in male rats during morphine withdrawal.

The biologically active substance P (SP) N-terminal metabolite SP(1-7) has been reported to modulate several neural processes such as learning, locomotor activity and reaction to opioid withdrawal. Although all these processes are believed to be associated with dopaminergic transmission no evidence of an interaction between SP(1-7) and dopamine in the case of morphine withdrawal has so far been reported. Therefore, in this work we applied in vivo microdialysis to investigate the effect of SP(1-7) injection into the ventral tegmental area on dopamine release in nucleus accumbens of male rats during naloxone precipitated morphine withdrawal. The result showed that the heptapeptide enhances dopamine release and also elevates the level of the dopamine metabolite dihydroxyphenylacetic acid in this brain area. It was suggested that the observed action of the SP fragment on the dopamine system represents the underlying mechanism for a previously observed ability of SP(1-7) to counteract the aversion response to morphine withdrawal.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2002

Dopaminergic effects after chronic treatment with nandrolone visualized in rat brain by positron emission tomography.

Anabolic-androgenic steroids (AAS) have recently been shown to induce neurochemical alterations in areas of the male rat CNS related to behavioural changes that have been observed among AAS misusers. In the present study, positron emission tomography (PET) is suggested as a suitable in vivo method in order to visualize the density of the dopamine transporter ([11C]-FE-beta-CIT) as well as the dopamine D1-like ([11C]-(+)-SCH23390) and the D2-like receptors ([11C]-raclopride) in the male rat brain. Chronic treatment with the AAS nandrolone decanoate (15 mg/kg/day for 14 days) caused an up-regulation of the binding potential of the dopamine transporter in the striatum.

Anabolic Agents↗

PubMed2002

The anabolic androgenic steroid, nandrolone decanoate, increases the density of Fos-like immunoreactive neurons in limbic regions of guinea-pig brain.

The increased abuse of anabolic androgenic steroids is a major concern because of physiological and psychological side-effects. In some individuals they induce dramatic behavioural changes such as increased aggression, anxiety and depression. The mechanisms behind these behavioural changes are still poorly understood. In order to obtain information on the brain regions affected by anabolic androgenic steroids, the distribution of neurons containing c-Fos, the protein product of the immediate early gene c-fos, and Fos-related antigens was studied following chronic treatment of guinea-pigs with a high dose of nandrolone decanoate (15 mg/kg i.m. daily for 14 days). The behaviour of the guinea-pigs was monitored for 1 h each day. Animals treated with nandrolone exhibited a significantly greater incidence of biting behaviour during the 14 day treatment period than vehicle-treated animals. A significantly greater density of c-Fos and Fos-related antigen-positive neurons was found in the central nucleus of the amygdala, and of Fos-related antigen-positive neurons in the frontal cortex, the shell of the nucleus accumbens and the supraoptic nucleus in nandrolone-treated animals than in vehicle controls. Therefore, nandrolone induced Fos in brain regions involved in stress, behavioural responses and reward. The increased Fos expression in these limbic brain regions is of particular interest in relation to the behavioural changes reported in humans who abuse anabolic androgenic steroids and the abuse potential of these drugs.

Aggression↗

PubMed1991

No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7.

The CSF levels of Met-enkephalin-Arg6-Phe7 and dynorphin A were measured in patients with fibromyalgia. The mean CSF Met-enkephalin-Arg6-Phe7 level was 35.1 +/- 2.4 fmol/ml (mean +/- S.E.M.). The mean CSF level of dynorphin A was 14.3 +/- 0.9 fmol/ml. Regression analysis showed a statistically significant correlation between Met-enkephalin-Arg6-Phe7 and dynorphin A (r = 0.5369, P = 0.001). When correlated to the previously measured CSF levels of beta-endorphin, a statistically significant correlation was found with Met-enkephalin-Arg6-Phe7 (r = 0.5055, P = 0.03) but not with dynorphin A (P greater than 0.05). The Met-enkephalin-Arg6-Phe7 and dynorphin A levels are elevated compared to the levels available for comparison groups. Therefore, a lack of endorphin secretion does not seem to be the basis for the hyperalgesia observed in these patients.

Adult↗

PubMed1990

Neuropeptide converting enzyme activities in CSF of low back pain patients.

The activity levels of a dynorphin converting enzyme (DCE), a substance P endopeptidase (SPE) and a substance P alpha-amidating enzyme (SP-GLYE) were measured in the cerebrospinal fluid (CSF) of 90 patients with chronic low back pain, sciatica and neurological signs of rhizopathy. The DCE activity was significantly higher in men than in women. Age was related to the DCE activity independent of sex, i.e., older patients had higher enzyme activity. The activities of two substance P converting enzymes were not related to sex or age. Self-reported pain experience and affective covariates (anxiety, depression, hostility, somatization) of pain, and myelography data were not found to be related to the enzyme activity levels once adjustment had been made for sex and age. The activity levels of the enzymes measured here had no predictive value for the long-term outcome of rehabilitation and therapy at the 5-year follow-up of the patients. The sex difference in DCE activity provides further evidence in favor of the role of gender in the psychoendocrine coping with pain distress.

Adult↗