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Hormones and the Dopamine System

Hormones and the Dopamine System

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Hormones and the Dopamine System

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  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 Glu DA GABA

  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 OVX+E OVX Amphetamine • E also has long term effects on AMPH-induced rotational behavior 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 OVX+E 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 MS=Male Saline FS=Female Saline MH=Male 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 Adam’s talk….

  28. Parkinson’s 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