Gonadectomy but not biological sex affects burst‐firing in dopamine neurons of the ventral tegmental area and in prefrontal cortical neurons projecting to the ventral tegmentum in adult rats. (19th September 2016)

• Record Type: Journal Article
• Authors: Locklear, Mallory N.; Michealos, Michalis; Collins, William F.; Kritzer, Mary F.
• Editors: Bolam, Paul
• Is Part Of: European journal of neuroscience. Volume 45:Number 1(2017)
• Page Start: 106
• Page End: 120
• Publication Date: 2016-09-19
• Subjects: androgen -- executive functions -- oestrogen -- reward -- substantia nigra; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13380
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: The mesocortical and mesolimbic dopamine systems regulate cognitive and motivational processes and are strongly implicated in neuropsychiatric disorders in which these processes are disturbed. Sex differences and sex hormone modulation are also known for these dopamine‐sensitive behaviours in health and disease. One relevant mechanism of hormone impact appears to be regulation of cortical and subcortical dopamine levels. This study asked whether this regulation of dopamine tone is a consequence of sex or sex hormone impact on the firing modes of ventral midbrain dopamine neurons. To address this, single unit extracellular recordings made in the ventral tegmental area and substantia nigra were compared among urethane‐anaesthetized adult male, female, gonadectomized male rats. These comparisons showed that gonadectomy had no effect on nigral cells and no effects on pacemaker, bursty, single‐spiking or random modes of dopamine activity in the ventral tegmental area. However, it did significantly and selectively increase burst firing in these cells in a testosterone‐sensitive, estradiol‐insensitive manner. Given the roles of prefrontal cortex (PFC) in modulating midbrain dopamine cell firing, we next asked whether gonadectomy's effects on dopamine cell bursting had correlated effects on the activity of ventral tegmentally projecting prefrontal cortical neurons. We found that gonadectomy indeed significantly and selectively increased burst firing in ventral tegmentally projecting but not neighbouring prefrontal cells. These effects were also androgen‐sensitive. Together, these findings suggest a working model wherein androgen influence over the activity of PFC neurons regulates its top‐down modulation of mesocortical and mesolimbic dopamine systems and related dopamine‐sensitive behaviours. Abstract : Single unit recordings made in ventral tegmental area dopamine neurons and in ventral tegmentally projecting prefrontal cortex cells were compared among urethane‐anaesthetized male, female and gonadectomized male rats. A survey of firing properties showed that gonadectomy selectively increased burst firing in both areas in a testosterone‐sensitive, estradiol‐insensitive manner. A working model is proposed for androgen impact originating in cortex and feeding forward to the ventral midbrain.