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Pharmacology JoVE (Open Access) Citable · DOI

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System

DOI: 10.3791/3956-v
What you'll learn
  • ✓ Perform pharmacological-challenge fMRI to assess serotonin neurotransmitter function in vivo
  • ✓ Administer intravenous SSRI challenge and acquire free-breathing MRI data in rodents
  • ✓ Preprocess and analyze phMRI datasets to detect drug-induced neural responses
  • ✓ Interpret pharmacological fMRI results to evaluate 5-HT system activity
Protocol

The goal of this technique is to assess serotonin (5-HT) neurotransmitter function in the live and free-breathing animal with pharmacological magnetic resonance imaging (phMRI) and an intravenous challenge with a selective serotonin reuptake inhibitor (SSRI), fluoxetine.

Difficulty
advanced
Total time
~2-3 hours per animal (including anesthesia induction, MRI acquisition, and drug challenge)
Model organism
Rodent (species not specified, likely rat or mouse)
Biosafety
BSL-1

Steps

1
Prepare animal and equipment for in vivo MRI imaging

Set up necessary instrumentation, anesthesia delivery systems, and physiological monitoring equipment for rodent MRI acquisition. Prepare the animal for secure positioning in the scanner.

▶ 01:50
2
Acquire baseline and pharmacologically-challenged fMRI data

Perform in vivo MRI scanning of the free-breathing animal, acquire baseline brain images, administer intravenous fluoxetine challenge, and continue acquisition to capture drug-induced neural responses.

▶ 03:15
3
Preprocess raw fMRI imaging data

Apply standard preprocessing steps including motion correction, registration to template space, and quality control filtering to prepare acquired MRI data for statistical analysis.

▶ 05:40
4
Perform statistical analysis of fMRI time-series data

Conduct voxel-wise statistical testing to identify brain regions showing significant responses to the pharmacological challenge, controlling for multiple comparisons.

▶ 06:55
5
Interpret pharmacological fMRI challenge results

Review activation maps and quantitative results demonstrating serotonin system engagement following SSRI administration, validating the phMRI technique for 5-HT assessment.

▶ 09:28
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