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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 62 (1985), S. 53-63 
    ISSN: 1435-1463
    Keywords: CNS ; development ; dopamine ; autoreceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The behavioural and biochemical effects of racemic 3-PPP (3-[3-hydroxyphenyl]-N-n-propyl-piperidine) and its enantiomers was studied in developing rats, aged 1–28 days. All three compounds exhibit dopamine (DA) autoreceptor-stimulating properties. Moreover, the (+)-enantiomer displays agonist and the (−)-enantiomer antagonist actions, respectively, on the postsynaptic DA receptor. This means that the racemate has a DA autoreceptor stimulatory action with slight or no effects on the postsynaptic receptor. Locomotor experiments demonstrated that (±)-3-PPP inhibited spontaneous locomotor activity dosedependently in the 28 days old rats. No effects were seen in the age groups 14 days and younger. While the racemate and the (−)-enantiomer inhibited spontaneous locomotor activity in 28 days old rats, the (+)-enantiomer had no effects compared to saline. Interestingly, the (+)-enantiomer increased locomotor activity in the 4 days old rats, while the (−)-enantiomer and the racemate did not induce any effects. In the biochemical experiments, after blockade of DA neurotransmission with gamma-butyrolactone (GBL), (±)-3-PPP inhibited the increase in tyrosine hydroxylase activity (DOPA accumulation after NSD 1015) after GBL in the DA rich striatum region of the 28 days but not of the 4 days old rats. From these experiments it may be concluded that functional postsynaptic but not presynaptic DA receptors exist in the brain af 4 days old rats. Presynaptic DA receptors do not seem to be functionally mature until 28 days postnatally in the rat, i.e. during adolescent age.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 49 (1980), S. 257-279 
    ISSN: 1435-1463
    Keywords: Rat brain ; ontogeny ; central 5-HT neurons ; transmitter metabolism ; nerve impulse activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Various characteristics of the developing serotoninergic system in the brain of rats aged 1 to 28 days were studied biochemically. The levels of the precursor amino acid tryptophan showed a maximal increase in the blood, brain and cerebrospinal fluid (CSF) during the 7th and 10th postnatal days. The development of tryptophan hydroxylase activity measuredin vivo by means of 5-hydroxytryptophan (5-HTP) accumulation after NSD 1015 was closely related to the 5-hydroxytryptamine (5-HT) levels at the various ages. 5-HTP accumulation and 5-HT levels increased most markedly after the second postnatal week. 5-Hydroxyindoleacetic acid (5-HIAA) levels were found to increase rapidly in the brain but somewhat more slowly in the CSF during the second week of postnatal development. Regional studies of 5-HTP accumulation after NSD 1015, 5-HT and 5-HIAA levels indicated a caudal to rostral way of maturation. The disappearance of 5-HT was measured after inhibition of tryptophan hydroxylase with H 22/54. The half-life generally decreased in the various brain parts with advancing age, and in the younger animals the shortest half-life was found in the most caudal brain parts. At 28 days of age the half-life was similar in all brain parts studied. These results indicate the existence of an adult like nerve impulse flow in the 5-HT neurons in the brain stem region of the newborn rats. The results from this investigation clearly indicate that the maturation of the different biochemical parameters of the 5-HT pathways develop in a caudal to rostral direction. The study also supports the view that tryptophan hydroxylase may be the limiting step in the development of the serotoninergic system.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 54 (1982), S. 19-28 
    ISSN: 1435-1463
    Keywords: Developing brain ; GHBA ; catecholamine mechanisms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gammahydroxybutyric acid (GHBA) was administered subcutaneously, 750mg/kg, to 1, 4, 14 and 28 days old rats 30 or 90 min before sacrifice. Whole brain and regional brain levels of tyrosine, dopamine (DA) and noradrenaline (NA) were measured. In some experiments the tyrosine hydroxylase activity was studied by measuring the accumulation of dihydroxyphenylalanine (DOPA) after inhibition of aromatic L-aminoacid decarboxylase. GHBA induced an increase in tyrosine and DA levels at the various ages except at 1 day of postnatal age. The effect of GHBA on the accumulation of DOPA after inhibition of aromatic L-aminoacid decarboxylase varied with age. Thus, tyrosine hydroxylase activity seemed to be enhanced in the 4 days old rats after 90 min and after 30 min in the 28 days old rats. Ninety minutes after GHBA administration to the 28 days old animals, DOPA accumulation reached or was slightly below control levels. Brain NA levels were not affected by GHBA administration. Regional analysis of DA and NA after inhibition of tyrosine hydroxylase withα-methyl-tyrosine demonstrated a reduced disappearance of DA after GHBA in the striatum region already from 4 days of postnatal age. GHBA administration did not affect the nerve impulse release of NA in any of the brain regions studied. It may be concluded that GHBA acts inhibitory on brain DA neurons during early postnatal development.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 59 (1984), S. 105-118 
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Various biochemical characteristics of the developing GABA system was studied in rats from 1 to 60 days of age. Endogenous GABA concentrations were high in the limbic system, midbrain, brain stem and spinal cord at birth. Until 7 days of postnatal age, GABA concentrations generally decreased, thereafter an increase was seen and at 60 days of age the GABA concentrations exceeded those found in the neonate except for the spinal cord regions. After GABA-T inhibition with AOAA, GABA concentrations increased in all brain regions, however considerably more marked in the 28 days old rats compared to the 4 days old animals. Turnover rate of GABA was estimated by investigating the rate of disappearance of GABA after GAD inhibition with 3-MPA. Calculated turnover time of whole brain GABA was 34.1 min in the 4 days old rats and 19.9 min in the 28 days old animals. The results from this investigation clearly indicate a caudal to rostral maturational gradient in the development of endogenous GABA concentrations as well as synthesis capacity. Furthermore, turnover rate of total whole brain GABA but probably not of GABA in the neuronal pool is retarded in the 4 days old rats compared to the adolscent animals.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 290-293 
    ISSN: 1432-1912
    Keywords: Adenosine ; Theophylline ; Enprofylline ; Antinociception ; Spinal mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The antinociceptive efects of the stable adenosine analogues N6-phenylisopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5′-N-ethylcarboxamindo-adenoxine (NECA) were investigated in conscious rats using cutaneous thermal tests (hot plate and tail flick). Subcutaneous administration of the adenosine analogues induced a dose-dependent antinociceptive response for all agents. However, NECA was approximately 15 times more potent than PIA and CHA. Approximately the same potency order and response was seen when the adenosine analogues were administered intrathecally at the lumbar level. By this route of administration, the adenosine analogues were approximately 10–20 times more potent than after S.C. administration. Intracerebroventricular administration (lateral ventricles), however, induced a variable response, in most cases a slight hyperalgesia. The nonspecific adenosine antagonist theophylline (S.C.) rapidly reduced the antinociceptive effect induced by PIA (S.C.) but enprofylline, a bronchodilating xanthine with low ability to antagonize adenosine did not influence PIA-induced antinociception. It is concluded that stable adenosine analogues and presumably adenosine itself have potent antinociceptive effects via specific adenosine receptors in the rat. The effects seem to be mediated mainly by a spinal mechanism of action.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 57 (1983), S. 39-48 
    ISSN: 1435-1463
    Keywords: Developing brain ; gammahydroxybutyric acid ; 5-HT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 5-HT synthesis, levels and degradation were investigated in the whole brain and regional brain areas in 4,14, and 28 days old rats after administration of gammahydroxybutyric acid (GHBA). 5-HT synthesis was investigated by means of 5-HTP accumulation after decarboxylase inhibition by NSD 1015. 5-HTP accumulation increased in the 14 and 28 days old rats but decreased in the 4 days old animals 90 min after GHBA, 750 mg/kg. In the 28 days old rats a corresponding increase was also noted in the precursor amino acid tryptophan. Regional and whole brain 5-HT levels were not altered by GHBA treatment. Regional as well as whole brain levels of 5-HIAA increased in the 14 and 28 days old rats after GHBA administration. In conclusion, the present data indicate that GHBA increases the synthesis and degradation of 5-HT in adolescent rats. These effects of GHBA were not seen in the neonatal animals.
    Type of Medium: Electronic Resource
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