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Hormones and the Dopamine System

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Title: Hormones and the Dopamine System


1
Hormones and the Dopamine System
  • Carey Stamps

2
Dopamine Neurons
Dopamine
Hormones
Neuroendocrine System
3
Dopamine Systems
1. nigrostriatal tract 2. mesolimbic tract 3.
mesocortical tract 4. tuberoinfundibular tract
4
Reward System
5
Dopamine Receptors
6
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

7
Brain Stimulation reward
Aka. Self-Stimulation, Intracranial
Self-stimulation, ICSS, BSR
8
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?
9
Amphetamine Rotation
10
Estrus Cycle
11
Estrus Cycle
  • Baseline changes in striatal dopamine

(Xiao, 1994)
12
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
13
OVX Effects
  • OVX attenuates dopamine (DA) release

14
Hormone Replacement
  • E2 treatment increases dopamine metabolites 4 hrs
    after application

(Fernandez-Ruiz, 1990)
15
Hormone replacement
  • E also has long term effects on AMPH-induced
    rotational behavior

Amphetamine
Apomorphine
(Hruska, 1980)
16
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)
17
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

18
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)
19
Estrogen and Drug Abuse
  • OVXE female rats
  • show a greater magnitude of sensitization
  • sensitize more quickly to cocaine
  • have higher CPP scores

(Hu, 2003)
20
Estrogen and Drug Abuse
  • Estrogen increases the rate of cocaine
    self-administration

(Lynch, 2005)
21
Sex Differences in Drug Abuse
  • Females acquire CPP with fewer sessions and at
    lower doses than males

(Russo, 2003)
22
Estrogen and Drug Abuse
  • Greater AMPH-induced release of striatal dopamime
    during estrus

estrus
diestrus
(Becker, 1989)
23
And for the Guys
  • Little evidence for the effect of testosterone on
    dopamine release.
  • sorry.

24
Antipsychotics
  • Impairs escape-avoidance behavior more in males
    than females

MSMale Saline FSFemale Saline MHMale
Haloperidol FH Female Haloperidol
(Parra, 1999)
25
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)

26
Human Drug Abuse
  • Most subjective, behavioral, and physiological
    effects of AMPH did not vary with menstrual
    cycle, except.

27
Schizophrenia
  • Stay tuned for Adams talk.

28
Parkinsons Disease
  • Neuroprotective maybe by inhibiting DA uptake
    by reducing DA transporter affinity

29
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

30
Future Directions
  • Further clarification of exactly which dopamine
    systems are influenced by hormones
  • HOW?!

31
Chromosomes v. Hormones
  • XX neuron cultures (regardless of gonadal
    phenotype) develop more DA neurons than XY
    cultures

(Arnold, 2004)
32
Other Hormones and Dopamine
LHRH produces condition place preference deBeun,
1991
CRF produces condition place aversion Cador, 1992
33
Estrogen in Males
  • Estrogen given to male rats increases striatal
    dopamine receptors

34
Mechanisms of Estrogen effects
1
2
E
Cortex
GABA
E
D2
Striatum or Accumbens
Substantia Nigra
Becker, 1999
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