Glu, Asp, GABA, Gly

1
???????????????? ? ????????????????

• ?????????? ????

2
????????? ??????????? ??????? ?? ????
????????????? ?? ????????? ??????????, ????????
????????????????. ???????? ?? ??? 100 ????
????????????????.

• ????? ????????
• ???????????
• ????????????? Glu, Asp, GABA, Gly
• ?????? ???
• ???????? ?????
• ???????????? ???????, ????????????, ?????????
• ?????????? ?????????
• ????????????? ????????
• ?????? ???????? ??????? 3-300??

3
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4
???????????

• ????? ?? ?????? ? ?????
• ???????????????????
• ???
• ?????????????? ???
• ???????????????? ??????? ?? ?????????? ???
• ?????-???????? ???????,
• ????? ?????
• ???
• ??????????? ????????

5
(No Transcript)
6
?????????

• ?????????? - ????? ?????? Na/K

• ??????????? G-??????? ???????? ?????????
  ??????? ????? ?????? ???? ???????? ?????????

7
???????

• ?????? - Chondodendron tomentosum
• ??????????? ?????? ??????
• ???????
• Betel nut - Areca catechu

• ???????
• ????????
• ????-????????????? Bungarus multicinctus nAchR

8
(No Transcript)
9
???????? ? ????????

• ????? ???????? ??????????? ????? ??????
  ???????? ??????? ? ??? ?? ???????????????

10

• - AMPA receptors a-amino-3-hydroxyl-5-methyl-4-iso
  xazole-propionate)
• - kainate receptors
• -NMDA receptors (N-?????-D-a???????) ?????????
  ? ??2 ???????? ????????? ?????? ?
  ????????????????? ????????? ?? ???????? ?? Mg2
  ?.?.????????? ?????? ???? ??? ????? ?????????????
  ??? ??????????? ??? ????????? ?? ?
  ???????????????? ??????? ??????
  LTR??????????? ? ???????????? ??????????
  ????????? ????? ???????
• Glutamate and other amino acids were first
  recognized as neurotoxins in the 1970s when these
  agents were given orally to immature animals.
  Acute neurodegeneration was observed in those
  areas not well protected by the bloodbrain
  barrier, notably the arcuate nucleus of the
  hypothalamus.
• The involvement of excitatory amino acids in
  epilepsy has been well documented. A large number
  of animal models of epilepsy have clearly
  implicated a causal role for the
  glutamate-receptor family (see Chap. 37).
  Excessive stimulation of glutamatergic pathways,
  block of glutamate transporters or
  pharmacological manipulation resulting in
  glutamate-receptor activation can precipitate
  seizures. Epileptiform activity usually begins
  with excessive AMPA receptor activation as
  seizure activity intensifies, an increased
  involvement of NMDA receptors is observed.
  Studies with a variety of animal models have
  shown that NMDA receptor antagonists can reduce
  the intensity and duration of seizure activity.
• Disorders of excitatory amino acid transmission
  have been implicated in amyotrophic lateral
  sclerosis (ALS)

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12
GABA ? Gly

• ??????????? ?????????
• GAD ?????????????? ?? ????-?? PLP
• ?????????
• ??????????? ? ? ?Cl-
• ?????????????
• Gly-??????????? ?? ???????? ?? ????????

13
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14
???????? ????? ????????????

• ???????
• ???????????? /????????????/
• ????????? /?????????/

15
(No Transcript)
16
???????

• Corpus striatum substantia nigra
• ?????????
• ??????????????
• G-??????? ????????? ?????????
• ?????? ??????? DAT(dopamine active transporter)
• ?????????? ???????? DAT ????????????????
  ?????????
• ??? ? COMT ?????????
• ??????????? ?? ? nucleus accumbens ? ventral
  tegmental area ??? ?????????? ???????????????
  experiences ???? ?????, ????, ????? ????????? ?
  ?????????? ? ??? ???????
• Opioid and cannabinoid transmission instead of
  dopamine may modulate consummatory pleasure and
  food palatability (liking).This could explain why
  animals' "liking" of food is independent of brain
  dopamine concentration.

17
???????????? ? ?????????

• ???/???????
• ????????
• ?????????? ?????????
• ????- ? ????- ???????????? ?????????
  (????????????)

18
(No Transcript)
19
????????? ? ????????
20

• ????????? (5-?????????????????)
• ???
• ??? ??????????????? (?????-?????????)
• ????????? ??????????? ??????? LNAA ???????????
  (????? ?? ????????? ??? ????? ??????? ?
  ??????????? ??????, ?? Trp ?????? ????? ????????)
• ?????????????
• 5-??-???????????? ?????????

21

• 5-?? ??????????? ???????? CRF-????,
  ?????????, ???????? ??????
• ????????????? ???? ?? ???????????? ????????
  ?????
• ????????? ?? ?????????? - arlylalkylamine
  N-acetyltransferase, ????????? ?? ?? ?????
• ???????? ? ???????????? ???????????? ???????,
  ????????? ???????, ???????? ????????

22
???/????????

• ???????????? ???????????????,
• ???????? ????????
• ?????????
• ???????????? 2 ???? ?? ??? ? ????????
• ?????????? ???????? ?????
• ???????? ???? ?????? ? ???????? ????????
  ??????????? ????????????? ???????

23
(No Transcript)
24
???????? ????????????????

• ????????? ???????
• ??????, ?????, ????? ? ?.?.
• ?????? ???-?????????? ?????????? ???????

25
(No Transcript)
26
??????? ? ???????? ?????????

• ??????????? ? ??????????? ??????? ?? ??????? ????
  70?? ?????? ?? ???.
• 4 ???? ?????????
• m
• d '92
• k
• ORL-1 (?rphan)
• G-??????? ?????????, ??????? K/???????? Ca2
  ??????

27
DISINHIBITION
28
????????? ???????

• ?????????
• ??????????
• ?????????

29
(No Transcript)
30
(No Transcript)
31
????????

• ???????? ?? ??????????????? ?? ??????????? ??
  ???????????????? ?-??????
• ?????????????? ?????????? ?? ????????? ?? ???????
  ??????, ????? ?????????? ????????? ???????
• ??? ???????????? ?? ??????? ?? ??????? ?? ???????
  ?? ?? ??????? ?????????? (?!)
• ?????? ???????????? ???????
• Reward system, ??????????????

32
???? ?? ?????????????

• ?????, ???. ???????
• ????????? ??????????
• ???????????
• ???????? ? ?? ??? ?? ?? ????? ??????? ??????
• ????? - ???? ??????? ?????!
• ?????????
• )))))))))))))))))))))))))))))))))))))))))

33
??????? ?????

• ??? ???? ???????-???????????? ????????? ???? ??
  ?? ??????? ?? ??????????? ????????, ????????
  ???????-??????????? ????? ?? ???????? ???????
  ???? ????????????? ?? ????????? ???? ??? ?
  ?????????? ??? ???????? ? ?????????, ?? ??
  ????????? ?????????? ????????????? ? ?? ??????? ?
  ????????? ?? ??????????, ????????? ?? ???????.
• They used PET brain scans of volunteers to
  record changes in activity of the brain's opioid
  system while the volunteers received a painful
  injection. The scans showed markedly increased
  activity of the endorphin/opioid system after the
  volunteers were told they were being given
  something that might ease the pain (though they
  weren't).

34
?????????? ?

• ???????? neurokinin
• ??????????? ????????, ??????????, ???, SC
• ?????, ?????????
• ??????????? ???????? SubP ??????????? ?????
• ????? ?????????????
• ??????

35
?????????

• ???????? ???????????, ????????? ?? ? ?????? ???
  ?? ?????????? (?????? ?? ?? ???????????????)
• ? ????? ?????????? ?? ??????? ????
• ? ??? ??????????? ???????? (G-??.???.)
• ????????, ??????? ?? ???????
• ??? ??????? ???????? ???????? ???? ?? ?????????
  (?????? ????)
• ??? ?????????? ??????? ???? ?? ??????? ???.??
  ????????? ? ????????

36

• Oxytocin secreted from the pituitary gland cannot
  re-enter the brain because of the blood-brain
  barrier. Instead, the behavioral effects of
  oxytocin are thought to reflect release from
  centrally projecting oxytocin neurons, different
  from those that project to the pituitary gland.
  Oxytocin receptors are expressed by neurons in
  many parts of the brain and spinal cord,
  including the amygdala, ventromedial
  hypothalamus, septum and brainstem.
• Sexual arousal ?????????? ? ???????????????
  ???????? ????????? ????????? ??????? ??? ???????
• Bonding - In the Prairie Vole, oxytocin released
  into the brain of the female during sexual
  activity is important for forming a monogamous
  pair bond with her sexual partner. Vasopressin
  appears to have a similar effect in males.
• ??????? ?? ???????
• ????????? ????????
• Increasing trust and reducing fear.
• MDMA (ecstasy) may increase feelings of love,
  empathy and connection to others by stimulating
  oxytocin activity via activation of serotonin
  5-HT1A receptors, if initial studies in animals
  apply to humans.ting generosity by increasing
  empathy during perspective taking