The extracellular concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum were measured by in vivo microdialysis in freely moving rats one week after the animals were treated with neurotoxic doses of methamphetamine. Methamphetamine produced a marked depletion of striatal DA measured in postmortem tissue, and in the extracellular concentrations of DOPAC, HVA and 5-HIAA. In contrast, the resting extracellular concentration of DA in striatum was the same as in saline-pretreated controls. Furthermore, methamphetamine-pretreated rats were able to increase their concentration of extracellular DA to the same extent as controls in response to a (+)-amphetamine challenge. It is suggested that this adaptive response is probably responsible, at least in part, for the absence of obvious behavioral deficits in animals exposed to neurotoxic doses of methamphetamine.
In vivo electrophysiological recording techniques were employed to examine responses of ventral pallidum/substantia innominata (VP/SI) neurons to systemic and local administration of morphine. Using a cumulative dosing protocol, intravenous administration (0.1-30 mg/kg i.v.) produced a suppression of firing in 82% of neurons tested. The suppression was dose-related and blocked by the opioid antagonist, naloxone. In contrast, microiontophoretic applications of morphine resulted in current-related suppression (32% of neurons tested) or excitation (26%). Concurrent application of naloxone attenuated or blocked both effects of local morphine application. It was demonstrated that acute tolerance did not develop with repeated morphine exposures following either systemic or local administration. The present findings establish the sensitivity of VP/SI neurons to morphine and provide functional relevance at the level of a single neuron for opioid peptides and their receptors in this region. As reported for most other opioid-receptive brain areas, neuronal rate suppression was the predominate response observed, and it is proposed that excitations to iontophoresed morphine reflect a disinhibitory phenomenon. The differential morphine-induced rate changes, and number of responding neurons, observed with systemic vs. iontophoretic morphine administration suggest that extra-VP/SI regions that also are opioid sensitive can subsequently direct neuronal responsiveness to opioids within the VP/SI.
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