Bi / CNS 150 Lecture 13 Monday, October 28, 2013 Recreational drugs Henry Lester This material is scattered throughout Kandel; see Nestler et al enzyme inhibitors neurotransmitter transport inhibitors http://site.ebrary.com/lib/caltech/docDetail.acti on?docID=10251590
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Bi / CNS 150 Lecture 13 Monday, October 28, 2013 Recreational drugsHenry Lester
neurotransmitter transport inhibitors. enzyme inhibitors. Bi / CNS 150 Lecture 13 Monday, October 28, 2013 Recreational drugsHenry Lester. This material is scattered throughout Kandel; see Nestler et al. http://site.ebrary.com/lib/caltech/docDetail.action?docID=10251590. Disclaimer - PowerPoint PPT Presentation
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Bi / CNS 150 Lecture 13 Monday, October 28, 2013
Recreational drugs Henry Lester
This material is scattered throughout Kandel; see Nestler et al
enzyme inhibitors neurotransmitter transport inhibitors
Hypothesis: the response to a drug requires your favorite molecule
Interrupt the gene with a detectable protein(knock out the gene)
EGFP
Replace the mouse gene with the altered gene
Select the mouse with the altered gene
Breed many identical mice measure drug response
vs
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Knockout mice in pharmacology(Behavioral observations)
1. The -opioid receptor-opioid receptor KOs specifically lack responses to certain types of pain (next slide).
2. The 42 nicotinic receptor4 or 2 nicotinic receptor knockouts:
(1) respond less to nicotine in pain tests (next slide)(2) fail to self-administer nicotine (next slide).
3. The dopamine transporterDopamine transporter knockout mice:
(1) are hyperactive, (2) show less response to cocaine, (3) self-administer cocaine less
4. Cannabinoid receptorsCannabinoid receptor knockouts have little overt differences to normal mice. They don’t show these effects of THC and anandamide: (1) decreased pain responses and (2) decreased heart rate.
---------------------------------------------------5. But NMDA receptor knockouts die at birth: an uninformative result
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Two behavioral tests often used on knockout mice
Pain:
Mice are placed on a hotplate at 55o C.
The experimenter notes the time to lick paws, jump, etc.
The experiment terminates at 30 s, regardless of the outcome.
A pain-relieving drug increases the time to react
No permanent harm to the mouse . . . Carefully regulated: