Imaging localised dynamic changes in the nucleus accumbens following nicotine withdrawal in rats

TY - JOUR

T1 - Imaging localised dynamic changes in the nucleus accumbens following nicotine withdrawal in rats

AU - Shoaib, Mohammed

AU - Lowe, Andrew S

AU - Williams, Steven

PY - 2004/6

Y1 - 2004/6

N2 - This study utilises pharmacological functional magnetic resonance imaging (fMRI) to examine the neurobiological mechanisms through which nicotine produces dependence. Using an established regime to induce physical dependence to nicotine in rats (osmotic minipumps delivering 3.16 mg/kg/day nicotine for 7 days SC), animals were subsequently anaesthetised under urethane and positioned in a stereotaxic frame to allow collection of gradient echo whole brain images with a 4.7-T MRI spectrometer. Rats were initially scanned for 34 min (40 baseline image volumes, 1 volume per 51 s) then challenged with mecamylamine (1.0 mg/kg SC) or saline (1 ml/kg) and scanned for a further 68 min (80 image volumes). Mecamylamine precipitated highly significant positive changes in fMRI blood oxygen level dependent (BOLD) contrast that were predominantly localised to the NAc of nicotine-dependent rats. Saline-treated rats challenged with the same dose of mecamylamine exhibited similar but smaller increases in BOLD contrast although such changes were less defined around the NAc. Precipitated withdrawal also elicited statistically significant negative BOLD contrast changes in widespread cortical regions. These findings are consistent with previous neurochemical reports on decreases in dopamine in the NAc during nicotine withdrawal. This fMRI study further highlights the potential and power to image the neurobiological events during nicotine dependence.

AB - This study utilises pharmacological functional magnetic resonance imaging (fMRI) to examine the neurobiological mechanisms through which nicotine produces dependence. Using an established regime to induce physical dependence to nicotine in rats (osmotic minipumps delivering 3.16 mg/kg/day nicotine for 7 days SC), animals were subsequently anaesthetised under urethane and positioned in a stereotaxic frame to allow collection of gradient echo whole brain images with a 4.7-T MRI spectrometer. Rats were initially scanned for 34 min (40 baseline image volumes, 1 volume per 51 s) then challenged with mecamylamine (1.0 mg/kg SC) or saline (1 ml/kg) and scanned for a further 68 min (80 image volumes). Mecamylamine precipitated highly significant positive changes in fMRI blood oxygen level dependent (BOLD) contrast that were predominantly localised to the NAc of nicotine-dependent rats. Saline-treated rats challenged with the same dose of mecamylamine exhibited similar but smaller increases in BOLD contrast although such changes were less defined around the NAc. Precipitated withdrawal also elicited statistically significant negative BOLD contrast changes in widespread cortical regions. These findings are consistent with previous neurochemical reports on decreases in dopamine in the NAc during nicotine withdrawal. This fMRI study further highlights the potential and power to image the neurobiological events during nicotine dependence.

KW - Rats, Inbred Strains

KW - Rats

KW - Animals

KW - Analysis of Variance

KW - Substance Withdrawal Syndrome

KW - Nicotine

KW - Nucleus Accumbens

KW - Kinetics

KW - Drug Implants

KW - Male

U2 - 10.1016/j.neuroimage.2004.01.026

DO - 10.1016/j.neuroimage.2004.01.026

M3 - Article

C2 - 15193614

SN - 1095-9572

VL - 22

SP - 847

EP - 854

JO - NeuroImage

JF - NeuroImage

IS - 2

ER -