Alcohol, allopregnanolone and aggression in mice

Fish, Eric W.; Faccidomo, Sara; DeBold, Joseph F.; Miczek, Klaus A.

doi:10.1007/s002130000587

Cited by 102 publications

(82 citation statements)

References 72 publications

(90 reference statements)

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“…Possibly low doses of progesterone are anxiogenic, whereas high doses have less anxiogenic effects or may even be anxiolytic. These hypotheses are supported by data from animal experiments in which low physiological doses of progesterone metabolites cause aggressive and aversive behavior but high dosages are inert or anxiolytic (23,24). In addition, during short-term treatment with physiologically relevant doses of progesterone in rats, a connection exists between progesterone-induced anxiety and upregulation of the a 4 subunit of the GABA A receptor in the hippocampus (25).…”

Section: Discussionmentioning

confidence: 88%

Progesterone effects during sequential hormone replacement therapy

Andréen

Bixo

Nyberg

et al. 2003

European Journal of Endocrinology

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Objective: The aim was to investigate the effect on mood and the physical symptoms of two dosages of natural progesterone and a placebo in postmenopausal women with and without a history of premenstrual syndrome (PMS). Design: A randomized, placebo-controlled, double-blind, crossover study was performed. Method: Postmenopausal women ðn ¼ 36Þ with climacteric symptoms were recruited. They received 2 mg estradiol continuously during three 28-day cycles. Vaginal progesterone suppositories with 800 mg/day, 400 mg/day, or placebo were added sequentially for 14 days per cycle. Daily symptom ratings using a validated rating scale were kept. Results: Women without a history of PMS showed cyclicity in both negative mood and physical symptoms while on 400 mg/day progesterone but not on the higher dose or the placebo. Women without a history of PMS had more physical symptoms on progesterone treatment compared with placebo. Women with prior PMS reported no progesterone-induced symptom cyclicity. Conclusion: In women without prior PMS natural progesterone caused negative mood effects similar to those induced by synthetic progestogens.

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Section: Discussionmentioning

confidence: 88%

Progesterone effects during sequential hormone replacement therapy

Andréen

Bixo

Nyberg

et al. 2003

European Journal of Endocrinology

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“…[47][48][49] Low doses of allopregnanolone increase aggressive behavior in mice, whereas higher doses decrease aggression. 50 Moreover, the addition of a low dose of progesterone to the treatment with estradiol during hormonal replacement therapy increases negative mood, but higher doses do not. 51 These negative mood symptoms are related to allopregnanolone levels in a bimodal fashion, as these symptoms are only present at moderate, but not low or high allopregnanolone concentrations.…”

Section: Discussionmentioning

confidence: 99%

Progesterone selectively increases amygdala reactivity in women

et al. 2007

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The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of c-aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies suggest that pregnanolone increases anxiety after a period of low allopregnanolone concentration. This effect is potentially mediated by the amygdala and related to the negative mood symptoms in humans that are observed during increased allopregnanolone levels. Therefore, we investigated with functional magnetic resonance imaging (MRI) whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli. The progesterone administration increased the plasma concentrations of progesterone and allopregnanolone to levels that are reached during the luteal phase and early pregnancy. The imaging results show that progesterone selectively increased amygdala reactivity. Furthermore, functional connectivity analyses indicate that progesterone modulated functional coupling of the amygdala with distant brain regions. These results reveal a neural mechanism by which progesterone may mediate adverse effects on anxiety and mood.

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“…Although this apparent discrepancy could be attributable to differences in the experimental paradigms used, recent studies suggest that it is more likely explained by differences in allopregnanolone concentration. Whereas allopregnanolone usually decreases anxiety in animal studies (Bitran et al, 1991;Wieland et al, 1991), moderate concentrations can increase aggressive behavior (Fish et al, 2001). Moreover, women who reach moderate allopregnanolone concentrations during hormonal replacement therapy develop negative mood symptoms more often than women reaching lower and higher concentrations (Andréen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The metabolite allopregnanolone potentiates the inhibitory effect of GABA by modulating the GABA A receptor (Majewska et al, 1986) and has been suggested to mediate the negative effects of progesterone on mood (NWihlbäck et al, 2006) and memory (Brett and Baxendale, 2001). Although allopregnanolone can also induce paradoxical effects at moderate concentrations (Fish et al, 2001;Andréen et al, 2006;, animal studies suggest that allopregnanolone usually decreases anxiety (Bitran et al, 1991(Bitran et al, , 1995Wieland et al, 1991) and impairs memory (Ladurelle et al, 2000;Johansson et al, 2002), suggesting a possible relationship between the effects of allopregnanolone on emotion and memory.…”

Section: Introductionmentioning

confidence: 99%

How Progesterone Impairs Memory for Biologically Salient Stimuli in Healthy Young Women

et al. 2007

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Progesterone, or rather its neuroactive metabolite allopregnanolone, modulates amygdala activity and thereby influences anxiety. Cognition and, in particular, memory are also altered by allopregnanolone. In the present study, we investigated whether allopregnanolone modulates memory for biologically salient stimuli by influencing amygdala activity, which in turn may affect neural processes in other brain regions. A single progesterone dose was administered orally to healthy young women in a double-blind, placebo-controlled, crossover design, and participants were asked to memorize and recognize faces while undergoing functional magnetic resonance imaging. Progesterone decreased recognition accuracy without affecting reaction times. The imaging results show that the amygdala, hippocampus, and fusiform gyrus supported memory formation. Importantly, progesterone decreased responses to faces in the amygdala and fusiform gyrus during memory encoding, whereas it increased hippocampal responses. The progesterone-induced decrease in neural activity in the amygdala and fusiform gyrus predicted the decrease in memory performance across subjects. However, progesterone did not modulate the differential activation between subsequently remembered and subsequently forgotten faces in these areas. A similar pattern of results was observed in the fusiform gyrus and prefrontal cortex during memory retrieval. These results suggest that allopregnanolone impairs memory by reducing the recruitment of those brain regions that support memory formation and retrieval. Given the important role of the amygdala in the modulation of memory, these results suggest that allopregnanolone alters memory by influencing amygdala activity, which in turn may affect memory processes in other brain regions.

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Alcohol, allopregnanolone and aggression in mice

Cited by 102 publications

References 72 publications

Progesterone effects during sequential hormone replacement therapy

Progesterone effects during sequential hormone replacement therapy

Progesterone selectively increases amygdala reactivity in women

How Progesterone Impairs Memory for Biologically Salient Stimuli in Healthy Young Women

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