Mapping of brain activation in response to pharmacological agents using fMRI in the rat

Functional MRI (fMRI) was used to investigate the effects of psychotropic compound activity in the rat brain in vivo. The effects of dizocilpine (MK-801) an N-methyl-D-aspartate receptor antagonist and m-chlorophenylpiperazine (mCPP), a 5-HT2b/2c-receptor agonist on rat brain activity were investigated over a time interval of about 1 h and the results were compared to published glucose utilisation and cerebral blood flow data. Signal magnitude increases were observed predominantly in limbic regions following MK-801 administration (0.5 mg/kg i.v) whereas signal decreases were restricted to neocortical areas; a characteristic, time dependent pattern of regional changes evolved from the thalamic nuclei to cortical regions. In contrast, mCPP (25 mg/kg i.p) produced gradual signal intensity increases in limbic and motor regions with signal decreases restricted to the visual, parietal and motor cortices. The results from both compounds show remarkable similarity with autoradiographic measurements of cerebral blood flow and glucose uptake. These experiments suggest that the spatio-temporal capabilities of fMRI may be applied to the in vivo investigation of psychoactive compound activity with potential for clinical applications.