Abstract

Repeated methamphetamine (mAMPH) damages forebrain monoamine terminals and causes degeneration of nonmonoaminergic cell bodies in rat primary somatosensory cortex (S1). These degenerating cortical neurons can be labeled with the fluorochrome dye Fluoro-Jade (FJ) and are found almost exclusively in layers II/III and IV of the vibrissae representation in S1. Within S1, layer IV is organized into discrete, anatomically identifiable units termed barrels, each of which receives information from a single whisker. We previously reported that mAMPH-damaged neurons in S1 were located within the whisker barrels, suggesting that the prolonged mAMPH-induced whisking contributes to S1 neuronal injury. Here, we investigate effects of vibrissae removal on mAMPH-induced damage to S1 neurons. Rats were anesthetized and vibrissae were trimmed from either the left, right, or neither side of the snout. The next day they were given four injections of either saline (1 ml/kg, s.c.) or mAMPH (4 mg/kg, s.c.) at 2-h intervals. Three days later, cortical sections were processed for FJ histochemistry. The hemivibrissotomy produces a hemispheric asymmetry in FJ-positive neurons in barrel cortex, with fewer damaged neurons contralateral than ipsilateral to whisker removal. Taken together with the demonstration that acute injection of this dose of mAMPH induces the immediate early gene zif/268 and Fos protein in barrel cortex, these data suggest that the prolonged behavioral activity involving the vibrissae contributes to the mAMPH-induced damage to S1 neurons. Thus, some of the injurious effects of drugs may depend on afferent activity occurring as a result of the abnormal behaviors evoked by their administration.

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