Hormones and the Dopamine System

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Hormones and the Dopamine System

• Carey Stamps

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Dopamine Neurons
Dopamine
Hormones
Neuroendocrine System
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Dopamine Systems
1. nigrostriatal tract 2. mesolimbic tract 3.
mesocortical tract 4. tuberoinfundibular tract
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Reward System
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Dopamine Receptors
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Methods

• Brain Stimulation Reward
• Conditioned Place Preference
• Behavioral methods of looking at reward rely on
  the animals actions to show levels of motivation
• Can be confounded by motor effects
• Amphetamine Rotation

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Brain Stimulation reward
Aka. Self-Stimulation, Intracranial
Self-stimulation, ICSS, BSR
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Conditioned Place Preference
Acclimation adjust environment so 50 of trial
is spent on each side
Trial 10 min
Conditioning 8 days of alternating drug and
saline treatment
D
S
d1
d2
Test - how much time is spent on each side?
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Amphetamine Rotation
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Estrus Cycle
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Estrus Cycle

• Baseline changes in striatal dopamine

(Xiao, 1994)
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Estrus Cycle

• During estrous female rats will self-stimulate in
  striatum significantly more than at any other pt.
  In the cycle
• Females will also increase prefrontal cortex
  self-stimulation at estrus (not as significant)

Steiner, 1982
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OVX Effects

• OVX attenuates dopamine (DA) release

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Hormone Replacement

• E2 treatment increases dopamine metabolites 4 hrs
  after application

(Fernandez-Ruiz, 1990)
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Hormone replacement

• E also has long term effects on AMPH-induced
  rotational behavior

Amphetamine
Apomorphine
(Hruska, 1980)
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Hormone Replacement

• E downregulates D2 receptor at 10 hr, increase at
  24 hr
• P decreases D2R at 4 hr but increases effect of E
  at 24 hr

(Fernandez-Ruiz, 1989)
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Conclusions Estrogen in the Striatum

• Dopamine release, reuptake, and metabolism is
  increased with endogenous surges of estrogen and
  progesterone
• Dopamine receptors (D2) are increased 24 hr
  following the surge

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But what does that have to do with?

• Estrogen in the striatum (and nucleus accumbens)
  enhances specific components of female sex
  behavior (ie. pacing and return latency)

(Becker, 1997)
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Estrogen and Drug Abuse

• OVXE female rats
• show a greater magnitude of sensitization
• sensitize more quickly to cocaine
• have higher CPP scores

(Hu, 2003)
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Estrogen and Drug Abuse

• Estrogen increases the rate of cocaine
  self-administration

(Lynch, 2005)
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Sex Differences in Drug Abuse

• Females acquire CPP with fewer sessions and at
  lower doses than males

(Russo, 2003)
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Estrogen and Drug Abuse

• Greater AMPH-induced release of striatal dopamime
  during estrus

estrus
diestrus
(Becker, 1989)
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And for the Guys

• Little evidence for the effect of testosterone on
  dopamine release.
• sorry.

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Antipsychotics

• Impairs escape-avoidance behavior more in males
  than females

MSMale Saline FSFemale Saline MHMale
Haloperidol FH Female Haloperidol
(Parra, 1999)
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In Humans
(why you care)

• Females are more sensitive than males to the
  reinforcing effects of drugs, particularly
  psychomotor stimulants. (Lynch, 2002)
• Human studies show that men have higher scores
  for thrill-seeking behaviors (Scourfield, 1996)

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Human Drug Abuse

• Most subjective, behavioral, and physiological
  effects of AMPH did not vary with menstrual
  cycle, except.

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Schizophrenia

• Stay tuned for Adams talk.

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Parkinsons Disease

• Neuroprotective maybe by inhibiting DA uptake
  by reducing DA transporter affinity

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Conclusions

• Estrogen increases striatal and accumbens
  dopamine release
• Estrogen causes females to be more sensitive to
  drug effects than males
• Estrogen is protective in diseases affecting DA
  release

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Future Directions

• Further clarification of exactly which dopamine
  systems are influenced by hormones
• HOW?!

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Chromosomes v. Hormones

• XX neuron cultures (regardless of gonadal
  phenotype) develop more DA neurons than XY
  cultures

(Arnold, 2004)
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Other Hormones and Dopamine
LHRH produces condition place preference deBeun,
1991
CRF produces condition place aversion Cador, 1992
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Estrogen in Males

• Estrogen given to male rats increases striatal
  dopamine receptors

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Mechanisms of Estrogen effects
1
2
E
Cortex
GABA
E
D2
Striatum or Accumbens
Substantia Nigra
Becker, 1999