Alterations in brain metabolism and function following administration of low-dose codeine phosphate: 1H-magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging studies

Abstract

The aim of the present study was to identify alterations in brain function following administration of a single, low-dose of codeine phosphate in healthy volunteers using resting-state functional magnetic resonance imaging (fMRI). In addition, the metabolic changes in the two sides of the frontal lobe were identified using ¹H-magnetic resonance spectroscopy (¹H-MRS). A total of 20 right-handed healthy participants (10 males, 10 females) were evaluated, and a Signa HDx 1.5T MRI scanner was used for data acquisition. An echo planar imaging sequence was used for resting-state fMRI, whereas a point resolved spectroscopy sequence was used for ¹H-MRS. Regional Saturation Technique, Data Processing Assistant for Resting-State fMRI, and Statistical Parameter Mapping 8 were used to analyze the fMRI data. The ¹H-MRS data were analyzed using LCModel software. At 1 h after oral administration of codeine phosphate (1.0 mg/kg), the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity were altered in different brain areas. The choline content was significantly increased in the right and left frontal lobes following codeine phosphate administration (P=0.02 and P=0.03, respectively), whereas the inositol content was significantly decreased in the left frontal lobe (P=0.02). There was no change in the glutamic acid content in the frontal lobes. In conclusion, the functions of different brain regions can be affected by a single, low-dose administration of codeine phosphate. The alterations in metabolite content in the two frontal lobes may be associated with changes in brain function, whereas the ALFF in the globus pallidus may have an effect on codeine phosphate addiction. Finally, glutamic acid may be useful in the estimation of codeine dependence.

Keywords: brain function; codeine phosphate; magnetic resonance spectroscopy; metabolite changes; resting-state functional magnetic resonance imaging.

Figure 1.

Brain areas with an abnormal amplitude of low-frequency fluctuation (ALFF) following a single oral administration of codeine phosphate (1.0 mg/kg) compared to images before administration. Red indicates increased ALFF and blue indicates decreased ALFF. The figure shows representative images from all of the subjects.

Figure 2.

Brain areas with abnormal regional homogeneity (ReHo) values following a single oral administration of codeine phosphate (1.0 mg/kg), compared with images before administration. Red indicates increased ReHo and blue indicates decreased ReHo. The figure shows representative images from all of the subjects.

Figure 3.

¹H-MR spectra from the same subject. Magnetic resonance spectroscopy maps of the right frontal lobe (A) prior to and (B) following oral administration of codeine phosphate (1.0 mg/kg), and the left frontal lobe (C) prior to and (D) following oral administration of codeine phosphate (1.0 mg/kg).