I= NEUROCHEMICAL AND NEUROPHARMACOLOGICAL STUDIES IN RATS FOLLOWING SINGLE AND REPEATED RESTRAINT STRESSES
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Title of Thesis
NEUROCHEMICAL AND NEUROPHARMACOLOGICAL STUDIES IN RATS FOLLOWING SINGLE AND REPEATED RESTRAINT STRESSES

Author(s)
Tahira Perveen
Institute/University/Department Details
Department of Biochemistry/ University of Karachi
Session
1995
Subject
Biochemistry
Number of Pages
265
Keywords (Extracted from title, table of contents and abstract of thesis)
rats, restraint stresses, tryptophan, brain serotonin, depression, behavioural deficits, serotonergic functions, midbrain, hindbrain, hypothalamus, cortex, tryptophan hydroxylase

Abstract
A considerable body of evidence points to the involvement of the neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) in the pathogenesis as well as treatment of depression. Stress life events precipitate depression. Parallel studies on experimental animals show that an uncontrollable stress situation increases brain 5-HT metabolism and precipitates behavioural deficits. Stress-induced behavioural changes in rats are often taken as an animal model of depression. It has been also reported that restraint induced behavioural deficits do not occur when the stress is given repeatedly suggesting adaptation to a stress schedule occurs. The present study concerns serotonergic functions in rat brain following adaptation to stress. Important findings of the study are as follows:

1 Single episode of 2h restraint decreased 24h cumulative food intake and growth rate. Open field activity monitored 24h after restraint also decreased. The behavioural deficits were not observed following 5 restraint periods of 2h/day. Restraint- induced increases of rectal temperature did not occur in rats restrained 2h/day for 5 days.

2.An episode of 2h restraint increased brain 5-HT metabolism in previously unrestrained rats but not in rats adapted to 5 restraint periods of 2h a day.

3.Injected tryptophan increased plasma levels of tryptophan more in unrestrained than restrained rats but injected tryptophan-induced increases of 5-HT and 5-HIAA were greater in the latter group.

4 Injected tryptophan increased plasma levels of tryptophan more in unrestrained than repeatedly restrained rats but injected tryptophan induced increases of 5-HT and 5-HIAA were comparable in the two groups.

5 An episode of 2h restraint increased 5-HT synthesis rate in the midbrain, hindbrain, hypothalamus, and cortex of previously unrestrained rats. Increases in the hippocampus and striatum were not significant. The episode of 2h restraint did not increase 5-HT synthesis rate in the midbrain, hindbrain, hypothalamus and cortex of repeatedly restrained, behaviourally adapted rats. On the other hand, 5-HT synthesis rate increased in the hippocampus and decreased in the striatum when rats adapted to 5 restraint periods of 2h/day were re-restrained on the 6th day.

6. 8-0H-DPAT, a 5-HT1A selective agonist, provoked greater 5-HT syndrome like behaviour in repeatedly restrained behaviourally adapted rats than in previously unrestrained rats. Conversely, 8-0H-DPA T-induced decreases of 5-HT metabolism were greater in the latter group.

The results tend to suggest that at least two factors vis (1) increased availability of tryptophan to the brain and (2) enhanced activity of 5-HT synthesizing enzyme (tryptophan hydroxylase) are involved in the enhancement of 5-HT metabolism following an acute episode of restraint stress. Restraint-induced increases of brain 5-HT metabolism do not occur in repeatedly restrained behaviourally adapted rats because adaptive changes occur both in the availability of tryptophan to the brain and activity of tryptophan hydroxylase in general. In view of clinical evidences it is suggested that an increase in hippocampal 5-HT synthesis rate may be involved in adaptation. A role of somatodendritic and postsynaptic 5-HT 1 A receptors in adaptation to stress is also discussed. The findings imply that drugs modulating particularly hippocampal 5-HT function may prove better antidepressants.

Download Full Thesis
4824.77 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
79.99 KB
2 1 Introduction 1
277.71 KB
3 2 Materials And Methods 36
274.14 KB
4 3 Behavioural Effect Of Single And Repeated Restraint 80
1105.14 KB
5 4 Effect Of 1h Restraint Stress On The Disposition And Metagolism Of Tryptophan In Plasma, Liver And Brain Of Previously Unrestrained And 5 Day (2h/Day) Restrained Rates 113
524.86 KB
6 5 Effect Of 2h Restraint Stress On The Disposition And Metagolism Of Tryptophan In Plasma, Liver And Brain Of Previously Unrestrained And 5 Day (2h/Day) Restrained Rates 130
480.73 KB
7 6 Effect Of Tryptophan Loan Ion Brain Serotonin Metabolism In Unrestrained And Restrained Rats 145
292.94 KB
8 7 Effects Of Tryptophan Administration On Metabolism Of Brain Serotonin In Previously Unrestrained And 6day (2h/Day) Restrained Rats 165
278.57 KB
9 8 Effect Of 2h Restraint Stress On Brain Regional 5-Ht Synthesis Rate In Previously Unrestrained And 5 Day (2h/Day) Restrained Rats 165
742.81 KB
10 9 Behavioural And Neurochemical Effects 8-Oh-Dpst In Previously Unrestrained And 5 Day (2h/Day) Restrained Rats 185
610.14 KB
11 10 Discussion 201
496.76 KB
  10.1 Implications 214
  10.2 Future Prospects 215
  10.3 References 216
  10.4 Publications From The Thesis 264