Neuronal activity of the medial prefrontal cortex, nucleus accumbens, and basolateral amygdala in conditioned taste aversion and conditioned place preference induced by different doses of morphine administrations in rats.

To re-examine the paradoxical effect hypothesis of abused drugs, the present study concerned whether different doses of morphine disparately affect neuronal activity and associations among the subareas of the medial prefrontal cortex (mPFC: cingulate cortex 1-Cg1, prelimbic cortex-PrL, infralimbic cortex-IL), the subregions of the nucleus accumbens (NAc; both core and shell), and the basolateral amygdala (BLA) following conditioned taste aversion (CTA) and conditioned place preference (CPP). All rats were given a 0.1% saccharin solution for 15-min, and they were intraperitoneally injected with saline or 20, 30, or 40 mg/kg morphine to form the aversive CTA learning. Later, half of the rats were tested for CPP (including the CTA and then CPP tests) for 30-min. Finally, the immunohistochemical staining with c-Fos was conducted after the behavioral test. After the CTA test, c-Fos (%) in the Cg1 and PrL (but not the IL) was more in 20-40 mg/kg of the morphine groups; c-Fos (%) in the NAc core, NAc shell, and BLA was more in the 30-40 mg/kg morphine group. After the CPP test, the Cg1, PrL, IL, and BLA showed more c-Fos (%) in 20 mg/kg morphine; the NAc core showed fewer in c-Fos (%) in the 30-40 mg/kg morphine groups. The mPFC subregions (e.g., Cg1, PrL, and IL), NAc subareas (e.g., NAc core and NAc shell), and BLA were involved in the different doses of morphine injections. The correlation analysis showed that a positive correlation was observed between PrL and IL with NAc core with low doses of morphine and with NAc shell with increasing doses of morphine after the CTA test. After the CPP, an association between PrL and NAc core and NAc shell at low doses and between IL and BLA and NAc shell with increasing doses of morphine. Therefore, different neural substrates and the neural connectivity are observed following different doses of morphine and after the CTA and CPP tests. The present data extend the paradoxical effect hypothesis of abused drugs.

Targeting brain-derived neurotrophic factor in the medial thalamus for the treatment of central poststroke pain in a rodent model.

Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. An animal model of CPSP was established by an intrathalamus injection of collagenase. Mechanical and thermal allodynia was induced after lesions of the thalamic ventral basal complex in rats. Four weeks after the injection, the number of neurons decreased, the number of astrocytes, microglia, and P2X4 receptors increased, and BDNF mRNA expression increased in the brain lesion area. Nociceptive activity in the medial thalamus (MT) and the coherence coefficient of spontaneous field potential oscillations in the anterior cingulate cortex were enhanced in CPSP animals, and these enhancements were blocked by an acute injection of TrkB-Fc and TrkB antagonist Tat Cyclotraxin-B. Instead of being inhibited by the γ-aminobutyric acid (GABA) system in normal rats, multiunit activity in the MT was enhanced after a microinjection of muscimol, a GABAA receptor agonist, in CPSP animals. After CPSP, BDNF expression was enhanced in the MT, whereas the expression of GABAA channels and the cotransporter KCC2 decreased in the same area. These findings suggest that neuronal plasticity in the MT that was induced by BDNF overexpression after the thalamic lesion was a key factor in CPSP.

Nocifensive behaviors components evoked by brief laser pulses are mediated by C fibers.

Nocifensive behavior involves several response elements that have been used to assess neuropharmacological effects in different animal models of pain. Our previous analysis of laser-evoked nocifensive behaviors suggested that hierarchically organized responses in the nocifensive motor system are recruited in varying degrees by noxious stimuli of different intensities. Nocifensive behaviors can be differentially elicited and mediated by different classes of nociceptors. Thus, the aim of this study was to test the hypothesis that nocifensive behavioral elements elicited by brief laser pulse stimuli are mediated by C nociceptors. Laser-evoked cortical potentials and nocifensive behavior elements were recorded concurrently. As stimulus energy increased, rats exhibited a larger number of different responses and a greater frequency of each response element. Applying the neurotoxin, capsaicin, which selectively inhibits C fibers, to the sciatic nerves of rats, differentially blocked nocifensive behavioral components of flinch, withdrawal and licking but not non-nocifensive responses, namely movement and head turning. Based on these results we suggest that flinch, withdrawal and licking are mediated by C fibers, which are temporally associated with the nocifensive motor system as well as spinal and cortical evoked potentials. These results link hierarchically organized nocifensive responses and the afferent C fibers in the nocifensive motor system.

BOLD response to direct thalamic stimulation reveals a functional connection between the medial thalamus and the anterior cingulate cortex in the rat.

Recent functional neuroimaging studies in humans and rodents have shown that the anterior cingulate cortex (ACC) is activated by painful stimuli, and plays an important role in the affective aspect of pain sensation. The aim of the present study was to develop a suitable stimulation method for direct activation of the brain in fMRI studies and to investigate the functional connectivity in the thalamo-cingulate pathway. In the first part of the study, tungsten, stainless steel, or glass-coated carbon fiber microelectrodes were implanted in the left medial thalamus (MT) of anesthetized rats, and T2*-weighted gradient-echo (GE) images were obtained in the sagittal plane on a 4.7 T system (Biospec BMT 47/40). Only the images obtained with the carbon fiber electrode were acceptable without a reduction of the signal-to-noise ratio (SNR) and image distortion. In the second part of the study, a series of two-slice GE images were acquired during electrical stimulation of the MT with the use of a carbon fiber electrode. A cross-correlation analysis showed that the signal intensities of activated areas in the ipsilateral ACC were significantly increased by about 4.5% during MT stimulation. Functional activation, as assessed by the distribution of c-Fos immunoreactivity, showed strong c-Fos expression in neurons in the ipsilateral ACC. The present study shows that glass-coated carbon fiber electrodes are suitable for fMRI studies and can be used to investigate functional thalamocortical activation.