The Serotonin Hypothesis of Major Depression - ACNP
Catecholamine hypothesis Permissive serotonin hypothesis GABA deficiency theory. What is the catecholamine hypothesis?
The Serotonin Hypothesis of Major Depression
We predicted that the serotonergic system would inhibit sex change, so we increased serotonergic activity in females in situations permissive to sex change. Unexpectedly, we found that female L. dalli show a trend for lower serotonergic function than males, so it makes sense that the manipulations did not have an effect on sex change because higher serotonergic function seems to be associated with male status. To exclude the possibility that in this species 5-HT might facilitate rather than inhibit sex change, we gave a PCPA implant to 4 dominant females in social groups permissive to sex change: after 3 weeks from male removal, the focal female had low brain 5-HIAA levels but nevertheless changed sex into male (Lorenzi unpublished data). Since these treatments did not have any effect we did not further pursue the hypothesis that serotonin might facilitate sex change.
According to this "permissive hypothesis", depression arises when low serotonin levels promote low levels of norepinephrine, another monoamine neurotransmitter ...
psychopathology chp 7 Flashcards | Quizlet
Though this hypothesis is still recognized, it does not explain everything, in particular why there are some people whose mood is not affected by fluctuations in their norepinephrine levels.
In the 1970s, the “permissive hypothesis” emerged, which postulated that another neurotransmitter, serotonin, was involved in depression.
In a variety of vertebrates, highly aggressive individuals tend to have high social status and low serotonergic function. In the sex changing fish Lythrypnus dalli, serotonin (5-HT) may be involved as a mediator between the social environment and the reproductive system because social status is a critical cue in regulating sex change. Subordination inhibits sex change in L. dalli, and it is associated with higher serotonergic activity in other species. We tested the hypothesis that high serotonergic activity has an inhibitory effect on sex change. In a social situation permissive to sex change, we administered to the dominant female implants containing the serotonin precursor 5-hydroxytryptophan (5-HTP). In a social situation not conducive to sex change, we administered either the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA) or the 5-HT1A receptor antagonist p-MPPI. After three weeks we used HPLC to measure brain levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA). We also performed PCPA, p-MPPI and fluoxetine injections in size-matched pairs of females to assess its effect on dominance status. Males and newly sex changed fish showed a trend for higher levels of 5-HIAA and 5-HT/5-HIAA ratio than females. The different implants treatments did not affect the probability of sex change. Interestingly, this species does not seem to fit the pattern seen in other vertebrates where dominant individuals have lower serotonergic activity than subordinates.
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Evaluation of the permissive amine theory
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