Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders.

Kuo, Chung-Chih and Chen-Tung Yen. Comparison of anterior cingulate and primary somatosensory neuronal responses to noxious laser-heat stimuli in conscious, behaving rats. J Neurophysiol 94: 1825-1836, 2005; 10.1152/jn.00294.2005. In this study, we investigated single-unit responses of the primary sensorimotor cortex (SmI) and anterior cingulate cortex (ACC) to noxious stimulation of the tail of the rat. The influences of morphine on these nociceptive responses were also compared. Multiple single-unit activities were recorded from two eight-channel microwire arrays chronically implanted in the tail region of the SmI and ACC, respectively. CO 2 laser-heat irradiation of the middle part of the tail at an intensity slightly higher than that causing a maximal tail flick response was used as a specific noxious stimulus. Examined individually, ACC neurons were less responsive than SmI neurons to laser-heat stimulus, in that only 51% of the ACC units (n ϭ 125) responded compared with 88% of the SmI units (n ϭ 74). Among these responsive ACC units, many had a very long latency and long-lasting excitatory type of response that was seldom found in the SmI. When ensemble activities were examined, laser heat evoked both short-(60 ϳ 150 ms) and long-latency (151 ϳ 600 ms) responses in the SmI and ACC. Latencies of both responses were longer in the ACC. Furthermore, a single dose of 2.5-10 mg/kg morphine intraperitoneally suppressed only the long latency response in the SmI, but significantly attenuated both responses in the ACC. These effects of morphine were completely blocked by prior treatment with the opiate receptor blocker, naloxone. These results provide further evidence suggesting that the SmI and ACC may play different roles in processing noxious information. I N T R O D U C T I O NRecent neuroimaging studies in human subjects have revealed several key forebrain areas most often activated by noxious stimulations. Among these areas are the primary somatosensory cortex (SI) and anterior cingulate cortex (ACC) (Casey et al. 1994; Coghill et al. 1994 Coghill et al. , 1999 Craig et al. 1996; Davis et al. 1995; Dorbyshire et al. 1997; Hsieh et al. 1995; Talbot et al. 1991; Vogt et al. 1996). Furthermore, studies by Rainville et al. (1997) and Hofbauer et al. (2001) showed that functional MRI (fMRI) intensities in the SI were correlated with the intensity of the noxious heat, whereas those in the ACC were better correlated with subjective unpleasantness, suggesting a differential functional role between SI and ACC.In contrast, the processing of nociceptive information in the forebrain at the cellular level is largely unclear. Neuroanatomical and neurophysiological studies have shown that pain information is processed through a complicated serial and parallel network in the forebrain (Craig 2003; Willis 1985). Electrophysiological studies of the SI have revealed nociceptive neu-

Evoked potential and ensemble neuronal activities were used to study the responses of the primary sensorimotor cortex (SmI) to noxious CO(2) laser irradiation of the middle part of the tail in conscious behaving rats. The hypothesis that systemic morphine treatment preferentially attenuates the longer-latency laser-evoked cortical responses was also tested. Laser-evoked potentials (LEPs) and multiple single-unit (SU) activities were, respectively, recorded from chronically implanted stainless-steel screws and microwire electrodes. When examined individually, many SmI neurons showed either short-latency (<100 ms) or long-latency (300-500 ms) responses to laser irradiation. These neurons are widely dispersed in the tail region and hind limb region of the SmI, and also in the forelimb and head regions of the primary motor cortex (MI). Quantitatively, a higher percentage of neurons in the SmI tail region responded with shorter latencies compared to those in the SmI hind limb region or in the MI. When responses of many simultaneously recorded SU were examined together, short-latency and long-latency SmI ensemble activities matched the LEP1 and LEP2, respectively. Systemic morphine significantly attenuated the long-latency but not the short-latency component in both LEPs as well as ensemble neuronal activity in the tail region of the SmI. These effects were blocked by naloxone pretreatment.

S ubthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be an effective treatment for advanced Parkinson's disease (PD) and yields good long-term motor outcome. 25 Conventionally, STN-DBS is a surgical procedure conducted while the patient receives a local anesthetic and remains awake to ensure accurate electrophysiological mapping. In addition, this approach allows physicians to conduct intraoperative macrostimulation tests for motor response while minimizing potential side effects of stimulation. However, if a patient with PD is experiencing drastic off-medication symptoms, such as anxiety, painful dystonia, and respiratory distress, the patient may be precluded from this lengthy surgical procedure. 16,26 We previously reported our long-term results describing patients with PD who underwent STN-DBS under conditioned general anesthe- (PD). However, few studies are available that report whether neuronal firing can be accurately recorded during this condition. In this study the authors attempted to characterize the neuronal activity of the subthalamic nucleus (STN) and elucidate the influence of general anesthetics on neurons during DBS surgery in patients with PD. The benefit of median nerve stimulation (MNS) for localization of the dorsolateral subterritory of the STN, which is involved in sensorimotor function, was explored. methods Eight patients with PD were anesthetized with desflurane and underwent contralateral MNS at the wrist during microelectrode recording of the STN. The authors analyzed the spiking patterns and power spectral density (PSD) of the background activity along each penetration track and determined the spatial correlation to the target location, estimated using standard neurophysiological procedures. results The dorsolateral STN spiking pattern showed a more prominent bursting pattern without MNS and more oscillation with MNS. In terms of the neural oscillation of the background activity, beta-band oscillation dominated within the sensorimotor STN and showed significantly more PSD during MNS (p < 0.05). coNclusioNs Neuronal firing within the STN could be accurately identified and differentiated when patients with PD received general anesthetics. Median nerve stimulation can enhance the neural activity in beta-band oscillations, which can be used as an index to ensure optimal electrode placement via successfully tracked dorsolateral STN topography.

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