Biomedical subjects

D J Haleem

Publications and source records attributed to D J Haleem.

11 recordsLinked to original sources

PubMed1995

24h withdrawal following repeated administration of caffeine attenuates brain serotonin but not tryptophan in rat brain: implications for caffeine-induced depression.

Caffeine injected at doses of 20, 40 and 80 mg/kg increased brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in rat brain. In view of a possible role of 5-HT in caffeine-induced depression the effects of repeated administration of high doses of caffeine on brain 5-HT metabolism are investigated in rats. Caffeine was injected at doses of 80 mg/kg daily for five days. Control animals were injected with saline daily for five days. On the 6th day caffeine (80 mg/kg) injected to 5 day saline injected rats increased brain levels of tryptophan, 5-HT and 5-HIAA. Plasma total tryptophan levels were not affected and free tryptophan increased. Brain levels of 5-HT and 5-HIAA but not tryptophan decreased in 5 day caffeine injected rats injected with saline on the 6th day. Plasma total and free tryptophan were not altered in these rats. Caffeine-induced increases of brain tryptophan but not 5-HT and 5-HIAA were greater in 5 day caffeine than 5 day saline injected rats. The findings are discussed as repeated caffeine administration producing adaptive changes in the serotonergic neurons to decrease the conversion of tryptophan to 5-HT and this may precipitate depression particularly in conditions of caffeine withdrawal.

Analysis of Variance↗

PubMed1994

Brain regional serotonin synthesis following adaptation to repeated restraint.

A single 2 h episode of restraint stress decreased food intake and growth rate of rats. These deficits were not observed after five restraint periods of 2 h a day, suggesting that adaptation occurred. An acute challenge with 2 h restraint increased 5-hydroxytryptamine (5-HT) synthesis rate in the cortex, hypothalamus, midbrain and hindbrain of previously unrestrained rats, but not those adapted to 5 days of 2 h daily restraint. Hippocampal and striatal 5-HT synthesis was not increased significantly by 2 h restraint in previously unrestrained rats but was increased and decreased, respectively, in rats exposed to five 2 h daily restraints, when they were restrained on the sixth day. The findings suggest an important role of 5-HT particularly in the hippocampus, in adaptation to stress.

5-Hydroxytryptophan↗

PubMed1994

Tolerance to diacetyl morphine antinociception: effects on brain serotonin.

The effects of 5 mg kg-1 diacetyl morphine (DAM) on brain serotonin metabolism of rats were investigated following tolerance to the antinociceptive effects of 2.5 mg kg-1 DAM. Brain levels of tryptophan and 5-hydroxy indoleacetic acid (5-HIAA) were higher in the DAM-tolerant rats killed 24 h after last daily administration of 2.5 mg kg-1 DAM. Administration of 5 mg kg-1 DAM produced less antinociception in DAM-tolerant than DAM-naive rats and increased brain tryptophan concentration in both tolerant and naive rats. 5-HIAA concentrations increased only in naive rats. Combined use of drugs interfering with brain 5-HT turnover along with opiates may be of future benefit for the treatment of chronic pain.

Analysis of Variance↗

PubMed1994

Decreases of plasma tryptophan concentrations following restricted feeding do not decrease serotonin and its metabolite in rat brain.

Rats trained on a restricted feeding (RF) schedule of 4 h/day were killed before (starved) and after (fed) the presentation of food to compare hepatic and brain tryptophan metabolism with feeding (FF) controls. The RF rats exhibited greater holo-tryptophan pyrrolase activity in the liver than FF controls. Holoenzyme activity of starved rats was greater than fed animals. Plasma levels of tryptophan higher in the FF rats were comparable in the starved and fed groups of RF rats. Plasma levels of glucose comparable in the FF and RF fed rats were smaller in the starved animals. Brain levels of tryptophan comparable in the RF fed rats and FF controls were smaller in RF starved rats. Brain concentrations of serotonin (5-hydroxytryptamine) and its metabolite 5-hydroxyindoleacetic acid comparable in the RF starved rats and FF controls were higher in the RF fed rats. Possible implication of the findings in the pathogenesis of food deprivation/starvation related disease, anorexia nervosa is discussed.

Animals↗

PubMed1994

Enhancement of hepatic tryptophan pyrrolase activity and decreases of open field locomotion following single and repeated administration of high doses of caffeine in rats.

In view of a possible role of kynurenine in caffeine-induced anxiety syndrome, the effects of single and repeated administration of caffeine on hepatic tryptophan (T)-pyrrolase activity are investigated. Single administration of caffeine at doses of 80 mg/kg decreased open field locomotion and increased hepatic T-pyrrolase activity. Locomotor stimulating effects of 80 mg/kg caffeine, monitored in the home cages of rats, were attenuated following daily administration of caffeine for 5 days. Open field locomotor activity of rats and its caffeine-induced decrement were also attenuated following 5 daily administrations of caffeine on the 6th day. Basal levels of hepatic T-pyrrolase activity increased after 5 daily administrations of caffeine on the 6th day. Acute administration of caffeine did not further elevate hepatic T-pyrrolase activity in 5 day caffeine injected rats. Drug adjuvants decreasing hepatic T-pyrrolase activity may prove valuable for extending the clinical utility of caffeine.

Animals↗

PubMed1992

Repeated corticosterone treatment attenuates behavioural and neuroendocrine responses to 8-hydroxy-2-(di-n-propylamino) tetralin in rats.

The effects of 5 day corticosterone treatment (50 mg/kg s.c.; 2 x daily) are investigated on the behavioural and neuroendocrine responses to a 5-HT-1A selective agonist, 8-hydroxy -2-(di-n-propylamino) tetralin (8-OH-DPAT) in rats. Daily corticosterone treatment decreased body weight and food intake. After 5 day treatment a drug challenge of 0.25 and 0.5 mg/kg 8-OH-DPAT given on the sixth day produced smaller forepaw treading but comparable head waeving, flat body posture and also hypothermia in 5 day corticosterone than 5 day saline injected rats. Hyperphagic effects of only 0.25 mg/kg 8-OH-DPAT were attenuated in 5 day corticosterone injected animals. The effects of 8-OH-DPAT on the increases of plasma corticosterone were markedly attenuated in the 5 day corticosterone injected animals. The findings may help towards an understanding of steroid-induced affective changes and psychosis.

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

PubMed1992

Sex differences in neurochemical and behavioural effects of 8-hydroxy-2-(di-n-propylamino) tetralin.

A number of neurochemical investigations have shown that 5-hydroxytryptamine (5-HT) metabolism and turnover is greater in females than male rats. However increased 5-HT metabolism does not necessarily imply greater 5-HT release at the functional post-synaptic sites. Pharmacological research based on 5-HT receptor stimulation therefore gained attention. Studies of this type are complicated because of the multiplicity of 5-HT receptors in the central nervous system. Chemical ligands may not have sufficient selectivity, to specifically bind to a single receptor population. Moreover, both the density and distribution of 5-HT receptors may follow a different pattern in male and female rats. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) is a centrally acting 5-HT agonist with a ligand binding profile showing selectivity towards 5-HT-1A receptor sites. The present article integrates research on neurochemical and behavioural effects of 8-OH-DPAT in male and female rats, in order to investigate sex-related differences in 5-HT-1A receptor dependent functions.

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

PubMed1990

Hippocampal 5-hydroxytryptamine synthesis is greater in female rats than in males and more decreased by the 5-HT1A agonist 8-OH-DPAT.

Brain regional 5-hydroxytryptamine (5-HT) and/or 5-hydroxyindoleacetic acid (5-HIAA) concentrations tended to be slightly higher in female rats than in males but differences were substantial only in the hippocampus where female values were 34% and 36% higher respectively. These findings were consistent with the synthesis rates of 5-HT as this was 53% greater in the female than in the male hippocampi. Other regions did not show significant sex differences. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 1 mg/kg sc) caused comparable decreases of 5-HT synthesis rate in both sexes and in all regions studied except the hippocampus where the percentage decrease was twice as large in the females (-64%) as in the males (-32%) so that the sex difference in 5-HT synthesis in this region largely disappeared. The results are discussed in relation to sex differences in behaviour and hippocampal function.

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

PubMed1990

Injected tryptophan increases brain but not plasma tryptophan levels more in ethanol treated rats.

In previous studies, long term treatment with ethanol has been shown to enhance brain 5-hydroxytryptamine 5-(HT) metabolism by increasing the activity of the regulatory enzyme tryptophan hydroxylase and or availability of circulating tryptophan secondarily to an inhibition of hepatic tryptophan pyrrolase. In the present study ethanol treatment given for two weeks decreased hepatic apo-tryptophan pyrrolase but not total tryptophan pyrrolase activity in rats. Tryptophan levels in plasma and brain did not increase significantly. But there was a marked increase of 5-HT but not 5-hydroxyindoleacetic acid (5-HIAA) concentration in brain, suggesting a possible increase in the activity of tryptophan hydroxylase. The effect of a tryptophan load on brain 5-HT metabolism was therefore compared in controls and ethanol treated rats. One hour after tryptophan injection (50 mg/kg i.p.) plasma concentrations of total and free tryptophan were identical in controls and ethanol treated rats, but the increases of brain tryptophan 5-HT and 5-HIAA were considerably greater in the latter group. The results are consistent with long term ethanol treatment enhancing brain serotonin metabolism and show that brain uptake/utilization of exogenous tryptophan is increased in ethanol treated rats and may be useful to understand the role and possible mechanism of tryptophan/serotonin involvement in mood regulation.

Animals↗

PubMed1989

8-OH-DPAT increases corticosterone but not other 5-HT1A receptor-dependent responses more in females.

The 5-HT1A receptor subtype agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (50-1000 micrograms/kg s.c.) dose dependently increased rat plasma corticosterone. Tube restraint for 30 min also increased plasma corticosterone; this effect was completely blocked by (-)-pindolol (1 mg/kg i.p.). Increases of corticosterone following either 8-OH-DPAT injection or restraint were significantly greater in female animals. The restraint stress-induced changes but not those due to 8-OH-DPAT were decreased by pretreatment with the tranquiliser chlordiazepoxide (10 mg/kg i.p.). In anaesthetized rats, restraint no longer significantly affected corticosterone levels but 8-OH-DPAT caused increases which (though much attenuated) were significantly greater in the females. Dose-dependent increases of plasma corticosterone also resulted on infusing 8-OH-DPAT (500-1500 ng) into the paraventricular nucleus of the hypothalamus; increases were significantly greater in the females. As mentioned in the discussion, these results may be relevant to the greater incidents of depression in women and the possible role of adrenal corticoids in the illness.

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

PubMed1988

Adaptation of female rats to stress: shift to male pattern by inhibition of corticosterone synthesis.

In a previous study, male rats showed behavioural deficits after a single restraint stress but not after 5 daily restraint periods (i.e. adaptation had developed): female rats although less affected by single restraint failed to adapt over the same time course. This sex difference was associated with the male but not the female rats showing enhanced behavioural responses to the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) after 5 restraint periods. In the present study, the role of the greater increases of plasma corticosterone in stressed females in these sex differences was studied. The corticosterone synthesis inhibitor metyrapone (75 mg/kg i.p.) was given to attenuate the rise of corticosterone to a level typical of stressed males. This resulted in the behavioural deficits of the female rats being shifted in the direction of the male pattern. Thus, their deficits in open field activity and food intake after single and repeated stresses were potentiated and opposed respectively. The latter effect was associated with increased responses to 5-MeODMT. Metyrapone alone was without significant effect. Brain regional 5-HT metabolism was unaffected. The results are consistent with corticosterone facilitating adaptation to single restraint but impairing adaptation to repeated restraint. As failure to adapt to repeated stress is an animal model of depression, results as a whole suggest that increased corticoid levels and decreased 5-HT functional activity may have a role in the development of the illness and its greater incidence in women.

Adaptation, Physiological↗