Techniques in Drug Admin

Pure Food and Drug Act (1906)

forbade sale of mislabeled food + drugs

Federal Food, Drug, and Cosmetic Act of 1938

mandated tests for drug toxicity + means for recall of drugs

3 phases of self administration

1. self-admin
2. extinction
3. reinstatement/relapse - cue, drug, stress

areas involved in drug self-admin (acquisition + expression)

STR, NAc, VTA, PFC

What are we looking for in the relapse phase?

- what brain area is activated
- what cue is shown
- is it critical for learning/expression
- can we block it

critical areas for motivation, reward, learning (+addiction)

1. VTA - ventral tegmental area
2. SNc - substantia nigra pars compacta
3. NAc - nucleus accumbens
4. CPu - caudate putamen
5. PFC - prefrontal cortex

**all DA-related*

basal ganglia

role in voluntary locomotion;
- input from cortex, output to brainstem via motor cortices

4 principle nuclei of the basal ganglia

1. striatum
2. globus pallidus
3. substantia nigra - DA > striatum
4. subthalamic nucleus - Glu output. stimulates SN

pars reticula

- GABA \> thalamus (inhibitory)
- GABA \> motor areas (inhibitory)

striatum (STR)

largest area in basal ganglia;
- GABAergic, DA receptors
- input from cortex + thalamus
- 96% spiny-neurons

globus pallidus

GABAergic, provides tonic inhibition
- can be disinhibited by STR input

positive feedback (GO)

output is enhanced

* direct pathway
* tonically inactive, disinhibits thalamus

negative feedback (NO GO)

some function of the output is fed back in a manner that reduces output

* indirect pathway
* tonically active, thalamus is constantly inhibited

balance of indirect/direct pathways

controls complex movements -> tonic inhibition/disinhibition

* ex. Parkinson's = lack of balance (less inhibition + less DA)
* treatment → L-DOPA (DA agonist)

C-Fos

an immediate early gene used to identify activated neurons
(is a nuclear protein)

immediate early gene

activate in response to cellular activity

* needed to facilitate late gene activity which requires proteins for transcription

C-Fos detection

ELISA method - way of tagging proteins w/antibody systems


1. primary anti-A binds to protein of interest
2. secondary binds to primary w/tag
3. allows proteins to be counted

immunohistochemistry pros + cons

**pros** - specificity, can label proteins + mRNA
**cons** - complex process, tissue not reusable, can't label multiple targets

ex. ELISA method

self-admin phase goes from...

start (acquisition) to finish (established/habitual behavior)

How do we test for acquisition vs. expression?

**acquisition** - manipulation __before__ training (ex. unplug)
**expression** - manipulation __after__ training