Anxiolytic Effects of Rapid Increases in Testosterone: Neuroendocrine Mechanisms and Functional Sign

1
Anxiolytic Effects of Rapid Increases in
Testosterone Neuroendocrine Mechanisms and
Functional Significance

• Aaron Lukaszewski
• PSY 235

2
What Causes Transient Increases in Circulating
Testosterone (T)?

• T increases in vertebrate males are reliably
  caused by exposure to mating opportunities (e.g.,
  Sipos Nyby, 2002)
• Estrous females
• Estrous female urine
• T spike facilitates mounting, intromission, and
  ejaculation.

3
Cost-Benefit Considerations

• Cost-Benefit structure of an organisms
  environment is in constant flux.
• E.g., Male vertebrates often face a trade-off
  between
• (i) Keeping safe from environmental hazards
  (predation, challenges from intrasexual
  competitors, etc.), and
• (ii) Mating (search, courtship, copulating)

4
The Costs of Mating

• Mating-associated activities increase
  vulnerability to hazards in at least 3 ways
• (i) mate search
• more time in open spaces (Krebs Davies, 1997)
• (ii) conspicuous courtship displays
• often sexually selected to be conspicuous by
  design (Andersson, 1994)
• (iii) diversion of attention from monitoring
  environment for cues to hazard (Aikey et al.,
  2002)

5
The Solution Facultative Design

• Costs of mating are in relation to its
  substantial potential benefit (producing a unit
  of fitness)
• Mechanisms designed to deal with this set of
  fluctuating contingencies might be expected to
• (i) maintain vigilance in most contexts, but
• (ii) down-regulate consideration of potential
  hazards when a mating opportunity arises
• i.e. decrease anxiety with respect to potential
  costs of mating

6
Reactive T Increases Do Indeed Have Anxiolytic
Effects in Rodents

• Aikey et al. (2002) house mice
• Used behavior on an elevated-plus
• maze as a measure of anxiety
• ( time spent in open arms is thought to
• correlate negatively w/ anxiety)
• T increases elicited via either (i) exposure to
  female stimuli, or (ii) T injections (at least
  250mg)
• ? decreased anxiety (more time spent in open arms)

7
Aikey et al. (contd)

• DHT, but not Estradiol, also caused anxiolysis.
• Implication T exerts its anxiolytic effect
  following 3a, 5a reduction.
• Indeed, androsterone and 3a androstanediol each
  proved to have a dose-response relationship with
  anxiety.
• Implication because these metabolites are weak
  androgens, but potent GABAA agonists, these
  results suggest that T-mediated anxiolysis occurs
  via GABAA receptors.
• Treatment with the GABAA antagonists picrotoxin
  (noncompetitive) or bicuccline (competitive)
  abolish the anxiolytic effects of T.

8
Localization?

• Edinger Frye (2005) Because the dorsal
  hippocampus expresses 5 and 3a reductase as well
  as GABAA receptors, it is a potential site of Ts
  anxiolytic action.
• Systemic and intrahippocampal injections of T,
  DHT, or 3a androstanediol reduced anxiety on 3
  measures
• (i) elevated-plus maze
• (ii) open field test ( entries into center
  squares / total square entries)
• (iii) defensive freezing in response to shock
• Also increased pain thresholds on two measures
• (i) latency to tailflick in response to the
  application of heat to the tail
• (ii) latency to pawlick when placed on a heated
  floor

9
Do human males express a homologous mechanism?

• Proposed function of T-mediated anxiolysis to
  increase willingness to be exposed to
  socio-ecological hazards
• But hazards differ by species
• Thus far, predator avoidance has been the primary
  function of rodent anxiety
• In humans, predation is a less significant
  problem (and should be less related to courtship,
  etc.)
• What function would such a mechanism serve in
  human males?

10
Do human males express a homologous mechanism?

• As in many non-human vertebrates, human males
  exhibit a rapid T increase in response to social
  interactions with young women (Roney, 2003 Roney
  et al., 2007)
• In human males, anxiety reduction during
  courtship may function to
• (i) increase display of behaviors that imply
  resource holding power, which are employed by
  women as mate choice criteria (Sadalla et al.,
  1987),
• (ii) increase actual willingness to engage with
  intrasexual competitors (Archer, 2006),
• (iii) cause men to discount the future (Wilson
  Daly, 2004)

11
(No Transcript)
12
Do human males express a homologous mechanism?

• van Honk et al. (2004)
• Injected women with T or vehicle
• Measured decisions on the IOWA gambling task
• Chose cards over 100 trials from 3 decks with
  varying payoff punishment ratios some
  riskier than others
• T-injected women chose significantly more cards
  from decks with bigger but less consistent
  payoffs than placebo-injected women
• Consistent with future discounting

13
Do human males express a homologous mechanism?

• van Honk et al. (2005)
• Injected women with T or vehicle
• Measured selective attention to fearful faces on
  an emotional stroop task
• Placebo-injected women showed an attentional bias
  for fearful faces, while T-injected women showed
  no such bias

14
Do human males express a homologous mechanism?

• Hermans et al. (2006)
• Injected women with T or vehicle
• Measured fear-potentiated startle response (via
  EMG)
• Contraction of the orbicularis oculi muscle (near
  the eye) in response to the threat of shock
• Startle response was elicited in all subjects,
  but its amplitude was lower over all eight blocks
  of trials in T-injected women than
  placebo-injected women.

15
Recap

• Transient T increases have anxiolytic effects in
  at least some male vertebrates (including humans)
• female stimulus mating opportunity ? rapid T
  increase ? 3a, 5a metabolites ? GABAA receptors ?
  increased willingness to confront environmental
  hazards anxiolysis

16
Future Directions

• Determine functions of female-induced T increases
  in human males
• Disentangle the effects of transient increases of
  T (reviewed above) from those of dispositional T
  level on male anxiety
• Stable individual differences traditional
  genomic mechanism?
• Reactive increases non-traditional genomic or
  non-genomic mechanism?

17

• Thanks!
• Acknowledgements
• -Me
• -OK..Kevin too.