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Scholarly Works (2 results)

  • Article
  • Peer Reviewed
UC San Diego Previously Published Works (2015)
Bipolar disorder is a unique illness characterized by fluctuations between mood states of depression and mania. Originally, an adrenergic-cholinergic balance hypothesis was postulated to underlie these different affective states. In this review, we update this hypothesis with recent findings from human and animal studies, suggesting that a catecholaminergic-cholinergic hypothesis may be more relevant. Evidence from neuroimaging studies, neuropharmacological interventions, and genetic associations support the notion that increased cholinergic functioning underlies depression, whereas increased activations of the catecholamines (dopamine and norepinephrine) underlie mania. Elevated functional acetylcholine during depression may affect both muscarinic and nicotinic acetylcholine receptors in a compensatory fashion. Increased functional dopamine and norepinephrine during mania on the other hand may affect receptor expression and functioning of dopamine reuptake transporters. Despite increasing evidence supporting this hypothesis, a relationship between these two neurotransmitter systems that could explain cycling between states of depression and mania is missing. Future studies should focus on the influence of environmental stimuli and genetic susceptibilities that may affect the catecholaminergic-cholinergic balance underlying cycling between the affective states. Overall, observations from recent studies add important data to this revised balance theory of bipolar disorder, renewing interest in this field of research.
    Cover page: The catecholaminergic–cholinergic balance hypothesis of bipolar disorder revisited
    • Article
    • Peer Reviewed
    International Journal of Comparative Psychology, Volume 14, Issue 3 (2001)

    Chronically elevated levels of corticotropin-releasing hormone (CRH) are implicated in human stress-related and affective disorders, including generalized anxiety disorder and major depression. To gain more insight into the relationship between hyperactivity of the CRH system and associated neuroendocrine, autonomic, physiological, and behavioral changes, we have developed a transgenic mouse model of CRH overproduction (CRHOE). In this study, we explored the behavioral consequences of chronic CRH overproduction in mice of the two available transgenic lines (CRH-OE2122 and CRH-OE2123) in paradigms measuring behavioral aspects of stress, anxiety, and depression. These paradigms include tasks based on free exploration of novel environments (unfamiliar homecage and unfamiliar open field), stress-induced hyperthermia, tests associated with anxiety- related behavior (elevated plus maze and light-dark box), and paradigms in which (anti-)depressant-like behaviors can be detected (tail suspension test and forced swim test). The only relatively consistent finding, although not always significant, was reduced locomotor activity in CRH-OE2122 mice, corresponding well with the known effects of CRH on locomotion. Contrary to our predictions, CRH-OE mice did not show an altered response to stress, and a phenotype indicative of increased anxiety and/or depression was not evident in CRH-OE mice.

      Cover page: Behavioral Analysis of Transgenic Mice Overexpressing Corticotropin-Releasing Hormone in Paradigms Emulating Aspects of Stress, Anxiety, and DepressionCreative Commons 'BY' version 4.0 license
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