Effects of aging on testosterone and androgen receptors in the mesocorticolimbic system of male rats

Low, Katelyn Laura; Tomm, Ryan J.; Ma, Chunsheng; Tobiansky, Daniel J.; Floresco, Stan B.; Soma, Kiran K.

doi:10.1016/j.yhbeh.2020.104689

Cited by 13 publications

(9 citation statements)

References 95 publications

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“…Sections were then placed on positively charged glass microscope slides for storage (−80°C) until microdissection. Microdissection using the Palkovits punch method 29,53,55,56 allows for collection of discrete brain regions 16 . We measured steroid levels in the lateral orbitofrontal cortex (LOFC), prelimbic region of the mPFC, NAc, dorsomedial striatum (DMS), and VTA (Figure S1).…”

Section: Methodsmentioning

confidence: 99%

“…Microdissection using the Palkovits punch method 29,53,55,56 allows for collection of discrete brain regions. 16 We measured steroid levels in the lateral orbitofrontal cortex (LOFC), prelimbic region of the mPFC, NAc, dorsomedial striatum (DMS), and VTA (Figure S1). We did not measure steroid levels in the medial orbitofrontal cortex (MOFC), since the region was too small to specifically target with our method.…”

Section: Steroid Extraction and Measurementmentioning

confidence: 99%

“…In reversal learning, an organism uses the same basic strategy, but must approach a previously-irrelevant cue within the same stimulus dimension to obtain a goal. [11][12][13][14] Importantly, androgen receptors (AR) are expressed in multiple regions of the mesocorticolimbic system, including the mPFC and OFC 15,16 as well as the ventral tegmental area (VTA) and nucleus accumbens (NAc).…”

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confidence: 99%

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Androgen synthesis inhibition increases behavioural flexibility and mPFC tyrosine hydroxylase in gonadectomized male rats

Tomm

Seib

Kachkovski

et al. 2022

J Neuroendocrinology

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Behavioural flexibility is essential to adapt to a changing environment and depends on the medial prefrontal cortex (mPFC). Testosterone administration decreases behavioural flexibility. It is well known that testosterone is produced in the gonads, but testosterone is also produced in the brain, including the mPFC and other nodes of the mesocorticolimbic system. It is unclear how testosterone produced in the brain versus the gonads influences behavioural flexibility. Here, in adult male rats, we assessed the effects of the androgen synthesis inhibitor abiraterone acetate (ABI) and long-term gonadectomy (GDX) on behavioural flexibility in two paradigms. In Experiment 1, ABI but not GDX reduced the number of errors to criterion and perseverative errors in a strategy set-shifting task. In Experiment 2, with a separate cohort of rats, ABI but not GDX reduced perseverative errors in a reversal learning task. In Experiment 1, we also examined tyrosine hydroxylase immunoreactivity (TH-ir), and ABI but not GDX increased TH-ir in the mPFC. Our findings suggest that neurally-produced androgens modulate behavioural flexibility via modification of dopamine signalling in the mesocorticolimbic system. These results indicate that neurosteroids regulate executive functions and that ABI treatment for prostate cancer might affect cognition.

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Section: Methodsmentioning

confidence: 99%

Section: Steroid Extraction and Measurementmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Androgen synthesis inhibition increases behavioural flexibility and mPFC tyrosine hydroxylase in gonadectomized male rats

Tomm

Seib

Kachkovski

et al. 2022

J Neuroendocrinology

Self Cite

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show abstract

“…Sections were then placed on positively charged glass microscope slides for storage (-80 ˚C) until micro-dissection procedures. Micro-dissection of the brain using the Palkovits punch method 28,[51][52][53] allows for collection and measurement of steroids in discrete brain regions 15 .…”

Section: Steroid Extraction and Measurementmentioning

confidence: 99%

“…Inactivation of the mPFC and OFC impair set-shifting and reversal learning [11][12][13] . Importantly, androgen receptors (AR) are expressed in multiple regions of the mesocorticolimbic system, including the mPFC and OFC 14,15 as well as the VTA and nucleus accumbens (NAc).…”

Section: Introductionmentioning

confidence: 99%

Androgen synthesis inhibition but not gonadectomy reduces persistence during strategy set-shifting and reversal learning in male rats

Tomm

Seib

Kachkovski

et al. 2021

Preprint

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Androgens regulate behavioural flexibility, which is essential to adapt to a changing environment and depends on the medial prefrontal cortex (mPFC). Testosterone (T) administration decreases behavioural flexibility. It is well known that T is produced in the gonads, but T is also produced in the mesocorticolimbic system, which modulates behavioural flexibility. It is unclear how T produced in the brain versus the gonads influences behavioural flexibility. Here, we assess the effects of the androgen synthesis inhibitor abiraterone acetate (ABI) and long-term gonadectomy (GDX) on behavioural flexibility in two paradigms. In Experiment 1, ABI independent of GDX reduced the number of trials to criterion and perseverative errors in a strategy set-shifting task. Similarly, in Experiment 2, ABI but not GDX reduced perseverative errors in a reversal learning task. In subjects from Experiment 1, we also examined tyrosine hydroxylase immunoreactivity (TH-ir), and ABI but not GDX increased TH-ir in the mPFC. Our findings suggest that neurally-produced androgens modulate behavioural flexibility via modification of dopamine signalling in the mesocorticolimbic system. These results suggest novel roles for neurosteroids and possible side effects of ABI treatment for prostate cancer.

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Improvement of testosterone deficiency by fermented Momordica charantia extracts in aging male rats

Lee

Kim

Park

et al. 2021

Food Sci Biotechnol

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Effects of aging on testosterone and androgen receptors in the mesocorticolimbic system of male rats

Cited by 13 publications

References 95 publications

Androgen synthesis inhibition increases behavioural flexibility and mPFC tyrosine hydroxylase in gonadectomized male rats

Androgen synthesis inhibition increases behavioural flexibility and mPFC tyrosine hydroxylase in gonadectomized male rats

Androgen synthesis inhibition but not gonadectomy reduces persistence during strategy set-shifting and reversal learning in male rats

Improvement of testosterone deficiency by fermented Momordica charantia extracts in aging male rats

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