Rat brain hypothalamic and hippocampal monoamine and hippocampal β-adrenergic receptor changes during pregnancy

The concentration of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites was measured in hypothalamic and hippocampal brain tissue obtained from non-pregnant, 15- or 20-day pregnant and 4-day postpartum rats. At 20 days of pregnancy, hypothalamic NA and DA concentrations were significantly decreased and their turnover increased relative to postpartum and estrous values, respectively. Hippocampal 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels were significantly decreased at 15 days of pregnancy and 4 days postpartum compared to estrous and 20-day pregnant levels and the MHPG/NA ratio was significantly reduced at 4 days postpartum relative to the estrous value. Hippocampal 5-HT and 5-hydroxyindole-3-acetic acid (5-H1AA) levels were significantly decreased at 15 days of pregnancy while 5-HIAA levels and the 5-HIAA/5-HT ratio were significantly decreased at 20 days of pregnancy. Hippocampal β-adrenergic receptor density was significantly lower at 4 days postpartum than at 15 days of pregnancy. A positive correlation was observed between plasma progesterone and hippocampal β-adrenoceptor K(d) values, suggesting a possible causal relationship between these two variables. The monoamine and β-adrenoceptor changes which occur during pregnancy may be an important contributing factor in determining the mood changes which occur during pregnancy and postpartum.The concentration of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites was measured in hypothalamic and hippocampal brain tissue obtained from non-pregnant, 15- or 20-day pregnant and 4-day postpartum rats. At 20 days of pregnancy, hypothalamic NA and DA concentrations were significantly decreased and their turnover increased relative to postpartum and estrous values, respectively. Hippocampal 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels were significantly decreased at 15 days of pregnancy and 4 days postpartum compared to estrous and 20-day pregnant levels and the MHPG/NA ratio was significantly reduced at 4 days postpartum relative to the estrous value. Hippocampal 5-HT and 5-hydroxyindole-3-acetic acid (5-H1AA) levels were significantly decreased at 15 days of pregnancy while 5-HIAA levels and the 5-HIAA/5-HT ratio were significantly decreased at 20 days of pregnancy. Hippocampal β-adrenergic receptor density was significantly lower at 4 days postpartum than at 15 days of pregnancy. A positive correlation was observed between plasma progesterone and hippocampal β-adrenoceptor K(d) values, suggesting a possible causal relationship between these two variables. The monoamine and β-adrenoceptor changes which occur during pregnancy may be an important contributing factor in determining the mood changes which occur during pregnancy and postpartum.ArticleArticl

Lack of effect of bilateral locus coeruleus lesion and antidepressant treatment on gamma-aminobutyric acid(B) receptors in the rat frontal cortex

The aim of the present study was to investigate whether a disturbance of the central noradrenergic (NA) system could cause changes in gamma- aminobutyric acid(B) (GABA(B)) receptors in the rat frontal cortex. Manipulation of the NA projection to the frontal cortex was achieved by bilateral lesion of the locus coeruleus with 6-hydroxydopamine (6-OHDA) or chronic treatment with the NA reuptake blocker and antidepressant drug, desipramine. Precautions were taken to ensure that the GABA(B) receptor assay was performed optimally and was not confounded by the presence of endogenously generated GABA. The results show conclusively that manipulation of the NA projection did not result in any significant change in the number (Bmax) or affinity (Kd) of GABA(B) receptors in the frontal cortex. These results do not support the hypothesis that hypoactivity of the central NA system can lead to changes in cortical GABA(B) receptors and that antidepressant drugs act by increasing GABA(B) receptor binding in the frontal cortex.The aim of the present study was to investigate whether a disturbance of the central noradrenergic (NA) system could cause changes in gamma- aminobutyric acid(B) (GABA(B)) receptors in the rat frontal cortex. Manipulation of the NA projection to the frontal cortex was achieved by bilateral lesion of the locus coeruleus with 6-hydroxydopamine (6-OHDA) or chronic treatment with the NA reuptake blocker and antidepressant drug, desipramine. Precautions were taken to ensure that the GABA(B) receptor assay was performed optimally and was not confounded by the presence of endogenously generated GABA. The results show conclusively that manipulation of the NA projection did not result in any significant change in the number (Bmax) or affinity (Kd) of GABA(B) receptors in the frontal cortex. These results do not support the hypothesis that hypoactivity of the central NA system can lead to changes in cortical GABA(B) receptors and that antidepressant drugs act by increasing GABA(B) receptor binding in the frontal cortex.ArticleArticl

Rat brain hypothalamic and hippocampal monoamine and hippocampal β-adrenergic receptor changes during pregnancy

The concentration of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites was measured in hypothalamic and hippocampal brain tissue obtained from non-pregnant, 15- or 20-day pregnant and 4-day postpartum rats. At 20 days of pregnancy, hypothalamic NA and DA concentrations were significantly decreased and their turnover increased relative to postpartum and estrous values, respectively. Hippocampal 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels were significantly decreased at 15 days of pregnancy and 4 days postpartum compared to estrous and 20-day pregnant levels and the MHPG/NA ratio was significantly reduced at 4 days postpartum relative to the estrous value. Hippocampal 5-HT and 5-hydroxyindole-3-acetic acid (5-H1AA) levels were significantly decreased at 15 days of pregnancy while 5-HIAA levels and the 5-HIAA/5-HT ratio were significantly decreased at 20 days of pregnancy. Hippocampal β-adrenergic receptor density was significantly lower at 4 days postpartum than at 15 days of pregnancy. A positive correlation was observed between plasma progesterone and hippocampal β-adrenoceptor K(d) values, suggesting a possible causal relationship between these two variables. The monoamine and β-adrenoceptor changes which occur during pregnancy may be an important contributing factor in determining the mood changes which occur during pregnancy and postpartum.The concentration of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites was measured in hypothalamic and hippocampal brain tissue obtained from non-pregnant, 15- or 20-day pregnant and 4-day postpartum rats. At 20 days of pregnancy, hypothalamic NA and DA concentrations were significantly decreased and their turnover increased relative to postpartum and estrous values, respectively. Hippocampal 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels were significantly decreased at 15 days of pregnancy and 4 days postpartum compared to estrous and 20-day pregnant levels and the MHPG/NA ratio was significantly reduced at 4 days postpartum relative to the estrous value. Hippocampal 5-HT and 5-hydroxyindole-3-acetic acid (5-H1AA) levels were significantly decreased at 15 days of pregnancy while 5-HIAA levels and the 5-HIAA/5-HT ratio were significantly decreased at 20 days of pregnancy. Hippocampal β-adrenergic receptor density was significantly lower at 4 days postpartum than at 15 days of pregnancy. A positive correlation was observed between plasma progesterone and hippocampal β-adrenoceptor K(d) values, suggesting a possible causal relationship between these two variables. The monoamine and β-adrenoceptor changes which occur during pregnancy may be an important contributing factor in determining the mood changes which occur during pregnancy and postpartum.ArticleArticl

Effect of corticosterone on noradrenergic nuclei in the pons-medulla and [3H]NA release from terminals in hippocampal slices

The aim of the present study was to investigate possible membrane and genomic effects of corticosterone on the noradrenergic system of the rat brain. Corticosterone effects were studied in vivo by treating rats s.c. with 10 mg/kg corticosterone for 7 or 14 days. In the first two experiments corticosterone significantly decreased the noradrenaline (NA) and dopamine (DA) levels in the pons-medulla, an area which contains the A1-A7 noradrenergic cell groups, while the NA and DA levels in the dorsal hippocampus remained unchanged. In a third experiment where the locus coeruleus (LC) and the A1 and A2 nuclei (A1,A2) were analysed separately, NA levels were unchanged but total MHPG levels and the total MHPG/NA ratio were decreased in the A1,A2 area. Chronic corticosterone treatment (14 days) did not alter the α2-adrenoceptor-mediated modulation of [3H]NA release from dorsal hippocampal slices. Neither the spontaneous outflow nor the electrically stimulated release of [3H]NA from dorsal hippocampal slices of untreated rats was affected by exposure of the slices to corticosterone (10-7 M - 10-4 M) in the superfusion buffer. Thus, chronic corticosterone treatment of rats altered the noradrenergic system of the pons-medulla, but did not change the α2-adrenoceptor-mediated modulation of NA release in the dorsal hippocampus, a major terminal area of the LC neurons. Corticosterone also did not appear to have a direct membrane effect on the NA terminals in the dorsal hippocampus of the rat.The aim of the present study was to investigate possible membrane and genomic effects of corticosterone on the noradrenergic system of the rat brain. Corticosterone effects were studied in vivo by treating rats s.c. with 10 mg/kg corticosterone for 7 or 14 days. In the first two experiments corticosterone significantly decreased the noradrenaline (NA) and dopamine (DA) levels in the pons-medulla, an area which contains the A1-A7 noradrenergic cell groups, while the NA and DA levels in the dorsal hippocampus remained unchanged. In a third experiment where the locus coeruleus (LC) and the A1 and A2 nuclei (A1,A2) were analysed separately, NA levels were unchanged but total MHPG levels and the total MHPG/NA ratio were decreased in the A1,A2 area. Chronic corticosterone treatment (14 days) did not alter the α2-adrenoceptor-mediated modulation of [3H]NA release from dorsal hippocampal slices. Neither the spontaneous outflow nor the electrically stimulated release of [3H]NA from dorsal hippocampal slices of untreated rats was affected by exposure of the slices to corticosterone (10-7 M - 10-4 M) in the superfusion buffer. Thus, chronic corticosterone treatment of rats altered the noradrenergic system of the pons-medulla, but did not change the α2-adrenoceptor-mediated modulation of NA release in the dorsal hippocampus, a major terminal area of the LC neurons. Corticosterone also did not appear to have a direct membrane effect on the NA terminals in the dorsal hippocampus of the rat.ArticleArticl

Effects of DSP-4 on monoamine and monoamine metabolite levels and on beta adrenoceptor binding kinetics in rat brain at different times after administration

Effects of DSP-4 on noradrenaline (NA), 3-methoxy-4-hydroxyphenyl glycol (MHPG), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) levels and on beta adrenoceptor binding kinetic (Bmax and K(D)) in rat hippocampus, cortex and hypothalamus were studied between 24 hours and 14 days after systemic administration. Beta adrenoceptor numbers in hippocampus and cortex, but not in hypothalamus, were significantly increased after DSP-4. No significant changes in K(D) value were observed in hypothalamus, but significant increases in this parameter were measured in hippocampus and cortex. NA and MHPG levels were significantly decreased in all three brain regions, but MHPG/NA ratios were increased in hippocampus, decreased in cortex and unchange in hypothalamus. Very prominent increases in 5-HIAA levels were observed in all three brain regions, but only at one day after DSP-4. The greatest increases in 5-HIAA levels occurred in the hippocampus, but this effect of DPS-4 appeared to be slightly diminished by pre-treatment with fluoxetine. In cortex and hippocampus 5-HT levels were slightly, but significantly decreased after DSP-4.Effects of DSP-4 on noradrenaline (NA), 3-methoxy-4-hydroxyphenyl glycol (MHPG), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) levels and on beta adrenoceptor binding kinetic (Bmax and K(D)) in rat hippocampus, cortex and hypothalamus were studied between 24 hours and 14 days after systemic administration. Beta adrenoceptor numbers in hippocampus and cortex, but not in hypothalamus, were significantly increased after DSP-4. No significant changes in K(D) value were observed in hypothalamus, but significant increases in this parameter were measured in hippocampus and cortex. NA and MHPG levels were significantly decreased in all three brain regions, but MHPG/NA ratios were increased in hippocampus, decreased in cortex and unchange in hypothalamus. Very prominent increases in 5-HIAA levels were observed in all three brain regions, but only at one day after DSP-4. The greatest increases in 5-HIAA levels occurred in the hippocampus, but this effect of DPS-4 appeared to be slightly diminished by pre-treatment with fluoxetine. In cortex and hippocampus 5-HT levels were slightly, but significantly decreased after DSP-4.ArticleArticl

Gamma-aminobutyric acid CSF

[No abstract available]Lette

Noradrenergic and dopaminergic modulation of thyrotropin secretion in the rat

Noradrenergic and dopaminergic regulation of thyrotropin (TSH) secretion was investigated in adult male Wistar rats. TSH secretion displayed a circadian variation with peak serum TSH levels at 10.00 h. The α2-adrenoceptor agonist, clonidine (250 μg/kg, i.p.), was found to cause an enhancement of serum TSH levels at 10.00 h (160 ± 10% of control values, P < 0.001) which was antagonized by prior administration of the α2-adrenoceptor antagonist, yohimbine (3 mg/kg, i.p.). The α-adrenoceptor antagonist phentolamine caused a significant decrease in serum TSH levels at 10.00 h (62 ± 15% of control values, P < 0.05) at a dosage of 2 mg/kg, i.p. The α1-adrenoceptor agonist, phenylephrine (0.2 or 2 mg/kg, i.p.), was without effect as were the dopaminergic receptor agonist, apomorphine (1 or 5 mg/kg, i.p.), and the antagonist, sulpiride (20 mg/kg, i.p.). The β-adrenoceptor agonist, isoproterenol (1 mg/kg, i.p.) was found to cause a decrease in serum TSH levels at 10.00 h (70 ± 16% of control levels, P < 0.01), which was completely antagonized by prior administration of the β-adrenoceptor antagonist, propranolol (10 mg/kg, i.p.).TSH-releasing hormone (TRH, 5 μg/kg, i.v.) caused a significant stimulation of TSH secretion (470 ± 63% of basal levels, P < 0.001), which was not affected by prior treatment of the rats with yohimbine (0.1 mg/kg, i.p.), phentolamine (2 mg/kg, i.p.), propranolol (10 mg/kg, i.p.) or sulpiride (20 mg/kg, i.p.). There was, however, a tendency towards a decrease in the TRH-stimulated release of TSH in rats pretreated with phentolamine or propranolol. The results of this study clearly demonstrate the existence of stimulatory α2-adrenoceptors as well as inhibitory β-adrenoceptors which modulate TSH secretion in vivo and which can be used to test noradrenergic receptor responsiveness under different pharmacological conditions.Articl

Decreased hippocampal noradrenaline does not affect corticosterone release following electrical stimulation of CA1 pyramidal cells

Bipolar electrodes were implanted into the CA1 pyramidal cells of the dorsal hippocampus and the effect of electrical stimulation of these cells on corticosterone secretion was investigated in freely moving rats. Histology showed that the electrodes were positioned in close proximity to the CA1 pyramidal cells. Rats that were subjected to high intensity electrical stimulation (1, 10, and 100μA) behaved differently when compared to their sham stimulated controls. They were more active and displayed wet dog shakes. Plasma corticosterone levels increased dose- dependently in rats subjected to different electrical stimulation intensities. Although prior treatment (24 hours) of rats with DSP4 (60 mg/kg, i.p.) significantly reduced hippocampal noradrenaline content by 46%, it did not bring about any behavioural changes. DSP4 treatment also had no effect on electrically stimulated corticosterone release. These data suggested that stimulation of CA1 pyramidal cells may lead to increased corticosterone release and that a decrease in hippocampal noradrenaline concentration was unable to alter this corticosterone response.Bipolar electrodes were implanted into the CA1 pyramidal cells of the dorsal hippocampus and the effect of electrical stimulation of these cells on corticosterone secretion was investigated in freely moving rats. Histology showed that the electrodes were positioned in close proximity to the CA1 pyramidal cells. Rats that were subjected to high intensity electrical stimulation (1, 10, and 100μA) behaved differently when compared to their sham stimulated controls. They were more active and displayed wet dog shakes. Plasma corticosterone levels increased dose- dependently in rats subjected to different electrical stimulation intensities. Although prior treatment (24 hours) of rats with DSP4 (60 mg/kg, i.p.) significantly reduced hippocampal noradrenaline content by 46%, it did not bring about any behavioural changes. DSP4 treatment also had no effect on electrically stimulated corticosterone release. These data suggested that stimulation of CA1 pyramidal cells may lead to increased corticosterone release and that a decrease in hippocampal noradrenaline concentration was unable to alter this corticosterone response.ArticleArticl

Regional effects of neurotensin on the electrically stimulated release of [3H]dopamine and [14C]acetylcholine in the rat nucleus accumbens

This study has shown that neurotensin (NT) increases the electrically stimulated release of [3H]DA to a similar extent in all but the extreme caudolateral area of the rat nucleus accumbens and appears to modulate DA release equally in the medial and lateral zones of this brain area. The simultaneous release of ACh was not significantly affected by NT.Articl

Cyclic AMP-arrhythmias. Myocardial maps and infusion

[No abstract available