Daniel Díaz Frutos

Modelos Preclínicos Máster Oficial Psicofarmacología

1. TECHNICAL DESCRIPTION OF THE APPARATUS

2. COMMON APLICATIONS

3. EXPERIMENTAL STUDIES OF INTERSPECIES

4. ADVANTAGES

5. DESADVANTAGES / LIMITATIONS

6. CLINICAL APPLICATIONS

7. ASSOCIATED BIOLOGICAL BASES

8. GENETIC BASIS

9. CONCLUSIONS

10. REFERENCES

INDEX

APPARATUS DESCRIPTION

•The five choice apparatus or “nine-hole box”

•Operant box

•Experiments

•5 choice testing

•Other apparatus

Number Description1 Nine 1 cm holes2 Food magazine3 Peristaltic pump4 Silicone tubing5 Microswitch6 Loudspeakers7 Houselights8 Electric fan9 Infrared-sensitive

camera

custom-built for mouse

The nine-hole box is commonly used to evaluate attention performance using a visual discrimination task in laboratory animals.

APPARATUS DESCRIPTION

•The five choice apparatus or “nine-hole box”

•Operant box

•Experiments

•5 choice testing

•Other apparatus

Number Description1 Nine 1 cm holes2 Food magazine3 Peristaltic pump4 Silicone tubing5 Microswitch6 Loudspeakers7 Houselights8 Electric fan9 Infrared-sensitive

camera

APPARATUS DESCRIPTION

Covert Orienting of Attention in the Rat and the Role of Striatal Dopamine (Ward, N. and Brown, V. 1996).

Twenty, pair-housed Lister hooded rats.

COMMON APPLICATIONS

The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry (Robbins, T. 2002).

The 5CSRTT: measuring effects of systemic drug treatments and also central manipulations such as neurochemical lesions on various aspects of attentional control, including sustained, selective and divided attention

COMMON APPLICATIONS

Deficits in Impulse Control Associated with Tonically-elevated Serotonergic Function in Rat Prefrontal Cortex (Dalley, J.,Theobald, D., Eagle, D., Passetti, M.D. and Robbins, T. 2002).

The subjects were 40 male Lister-Hooded rats

COMMON APPLICATIONS

Training to criterion

Surgery

Habituation

Surgery II

In-vivo Mycrodialysis

Post-Morten Analysis

Assaying Aspects of Attention and Impulse Control in Mice Using the 5‐Choice Serial Reaction Time Task (Humby, T., Wilkinson, L. and Dawson, G. 2005).

COMMON APLICATIONS

EXPERIMENTAL STUDIES OF INTERSPECIES

Rats experiments (Robbins, T. 2002; Dalley, J.,Theobald, D., Eagle, D., Passetti, M.D. and Robbins, T. 2002).

Mouse experiments (Bensadoun, J.C., Brooks, S, and Dunnett, S. 2004; Humby, t., Wilkinson, L. and Dawson, G. 2005).

Monkeys (Robbins, 2002, p. 376).

ADVANTAGES

Nose poke paradigms may be the most appropriate for measuring reaction times in rats

attention, covert orienting, impulsivity…

Powerful experimental tools to understand the pathological mechanisms involved in neurodegenative disorders.

To demonstrate considerable specificity of effects of thedifferent systems.(Robbins, T. 2002; Dalley, J.,Theobald, D., Eagle, D., Passetti, M.D. and Robbins, T. 2002; Bensadoun, J.C., Brooks, S, and Dunnett, S. 2004; Humby, T., Wilkinson, L. and Dawson, G. 2005)

LIMITATIONS / DISADVANTAGES

The main test requires a specialized multichoice apparatus and also involves several distinct indices of performance

Used in humans in another form, but probably needs further exploration to isolate distinct processes of attention.

Robbins, T. 2002; Dalley, J.,Theobald, D., Eagle, D., Passetti, M.D. and Robbins, T. 2002; Bensadoun, J.C., Brooks, S, and Dunnett, S. 2004; Humby, T., Wilkinson, L. and Dawson, G. 2005)

CLINICAL APPLICATIONS

Continuous performance tests (ADHD and Schizophrenia).

Alzheimer’s, Parkinson´s, Huntington´s deasease.

Drug abuse and withdrawal.

Covert orienting

Robbins, T. 2002; Dalley, J.,Theobald, D., Eagle, D., Passetti, M.D. and Robbins, T. 2002; Bensadoun, J.C., Brooks, S, and Dunnett, S. 2004; Humby, T., Wilkinson, L. and Dawson, G. 2005)

ASSOCIATED BIOLOGICAL BASES

Noradrenergic systems Accuracy

Dopaminergic systems Attention

Serotoninergic systems Impulsivity

Cholinergic systems Cognitive and attentional processes

Robbins, T. 2002; Dalley, J.,Theobald, D., Eagle, D., Passetti, M.D. and Robbins, T. 2002; Bensadoun, J.C., Brooks, S, and Dunnett, S. 2004; Humby, T., Wilkinson, L. and Dawson, G. 2005)

GENETIC BASIS

The recent identification of genetic mutations in some neurodegenerative disorders, including Parkinson’s and Huntington’s diseases has led to the rapid development of genetically modified mice with the aim of closely recapitulating the human condition.

Robbins, T. 2002; Dalley, J.,Theobald, D., Eagle, D., Passetti, M.D. and Robbins, T. 2002; Bensadoun, J.C., Brooks, S, and Dunnett, S. 2004; Humby, T., Wilkinson, L. and Dawson, G. 2005)

CONCLUSIONS

The development of the 9 hole box or ”5 choice task”:

Inspired by the problems of measuring changes relevant to clinical population such as ADHD and neurodegenerative disorders .

Methodological lead to investigate a number of operational measures of behavior such as attention and impulsivity.

Robbins, T. 2002; Dalley, J.,Theobald, D., Eagle, D., Passetti, M.D. and Robbins, T. 2002; Bensadoun, J.C., Brooks, S, and Dunnett, S. 2004; Humby, T., Wilkinson, L. and Dawson, G. 2005)

REFERENCES

Bensadoun, J.C., Brooks, S, and Dunnett, S. 2004. Free operant and discrete trial performance of mice in the nine- hole box apparatus: validation using amphetamine and scopolamine. Psychopharmacology, 173, 396-405

Humby, T., Wilkinson, L. and Dawson, G. 2005. Assaying Aspects of Attention and Impulse Control in Mice Using the 5‐Choice Serial Reaction Time Task.

Dalley, J.,Theobald, D., Eagle, D., Passetti, M.D. and Robbins, T. 2002. Deficits in Impulse Control Associated with Tonically-elevated Serotonergic Function in Rat Prefrontal Cortex, Neuropsychopharmacology, 26, 716-728.

Robbins, T. 2002. The 5-choice serial reaction time task: behavioural pharmacology and functional eurochemistry. Psychopharmacology, 163,362-380.

Ward, N.M., & Brown, V.J. 1996. Covert orienting of attention in the rat and the role of striatal dopamine. Journal of Neuroscience, 16, 3082-3088.

REFERENCES