Imaging cocaine-induced changes in the mesocorticolimbic dopaminergic system of conscious rats

Abstract

Functional magnetic resonance imaging (fMRI) was used to assess the effects of cocaine on brain activation in fully conscious rats. Methods were developed to image cocaine-induced changes in blood-oxygen-level-dependent (BOLD) signal without the peripheral cardiac and respiratory complications associated with psychostimulant administration. Using spin echo planar imaging (EPI), conscious rats were imaged in a 4.7 T spectrometer prior to and following the intracerebroventricular injection of cocaine (20 microg) in artificial cerebrospinal fluid (10 uL). Within 5 min of injection, there was a significant increase in BOLD signal intensity in the substantia nigra, ventral tegmental area, nucleus accumbens, dorsal striatum and prefrontal cortex, as compared to vehicle controls. Minimal negative BOLD signal changes were observed in response to cocaine and no significant perturbations in normal cardiovascular and respiratory function. These findings demonstrate the technical feasibility of studying psychostimulant-induced brain activity using functional MRI in conscious rats.

Functional Magnetic Resonance Imaging Shows Oxytocin Activates Brain Regions Associated with Mother–Pup Bonding during Suckling

“…]ornithine vasotocin (OTA) (Sigma, Natick, MA) were made via the intracerebroventricular (ICV) route while the animal was inside the magnet. Both chemicals were diluted in artificial CSF and injected at a dose of 1 g per 10 l. The rationale and methods for ICV injections in rats during functional MRI has been described in detail previously (Febo et al, 2004). The ICV dose of oxytocin is twice the amount necessary to induce maternal behaviors in the virgin rat (Pedersen and Prange, 1979), and the dose of OTA has been shown to occupy most central oxytocin receptors for 6 h or more (Witt and Insel, 1991).…”

“…Studies were performed using a multiconcentric dual-coil small animal restrainer (Insight NeuroImaging Systems, Worcester, MA), and described in detail in Ludwig et al (2004). Before breeding, females were acclimated to the restrainer and the imaging protocol as described previously by Febo et al (2004). Briefly, animals were lightly anesthetized with 2% isoflurane and secured into the dualcoil restrainer.…”

The Neural Consequences of Repeated Cocaine Exposure Revealed by Functional MRI in Awake Rats

“…Prior to imaging studies, animals were acclimated to the restrainer and the imaging protocol as described previously by Febo et al (2004). Briefly, animals were lightly anesthetized with 2% isoflurane and secured into the dual-coil restrainer.…”

“…The dose of cocaine used was 20 mg dissolved in 10 ml of artificial cerebrospinal fluid. The injection route and dose have been shown to reduce cardiac and respiratory complications associated with peripheral psychostimulant administration (Febo et al, 2004). Immediately prior to imaging, rats were anesthetized under 2% isoflurane, the skull surface was exposed and the landmark suture Bregma located.…”

“…Increased oxygenation of these areas contributes to the elevations in BOLD signal intensity (Thompson et al, 2003). An acute cocaine injection increases cerebral metabolic activity (Porrino, 1993) and blood flow (Stein and Fuller, 1992); effects that are likely to contribute to changes in BOLD signal intensity (Febo et al, 2004). These alterations could possibly involve effects of cocaine on synaptic monoamine levels throughout cortical and subcortical structures (Goeders and Smith, 1983;Kalivas and Duffy, 1993).…”