Kappa-opioid receptor activation prevents alterations in mesocortical dopamine neurotransmission that occur during abstinence from cocaine
Section snippets
Animals
Male Sprague–Dawley rats (Charles River Laboratories) weighing 250–350 g were housed in groups of three per cage for at least one week before use. They were maintained in a temperature- and humidity-controlled environment under an artificial 12 h/12 h light–dark cycle with laboratory rat chow and water available ad libitum. Animals used in this study were maintained in facilities accredited by the American Association for the Accreditation of Laboratory Animal Care (AAALAC), and all experiments
Histology
The placement of the microdialysis probes in the mPFC is illustrated in Fig. 1. The active 2 mm portion of each probe is shown. All probe placements with more than 25% of the dialysis membrane located outside the mPFC were excluded from the data analysis and are not shown here. On average, histological analysis confirmed correct placement of the microdialysis probes in 95% of the animals. There was no systematic group difference in histological placement of the microdialysis probes.
Influence of U-69593 pretreatment in combination with saline or cocaine upon cocaine-evoked locomotor activity
Discussion
This study demonstrates that the early phase of abstinence from cocaine is associated with an elevation of basal DA uptake in the mPFC and a blunted response of mesocortical DA neurons to a subsequent cocaine challenge. The co-administration of the selective kappa-opioid receptor agonist U-69593 with cocaine prevents these changes in prefrontal DA neurotransmission, and it is effective in preventing the sensitized behavioral response to cocaine that develops as a consequence of repeated drug
Conclusions
The present study demonstrates that basal and cocaine-evoked mPFC DA dynamics are altered during the early phase of abstinence from cocaine. The systemic administration of a selective kappa-opioid agonist prevents these changes in DA neurotransmission and the development of sensitization to the psychomotor stimulant effects of cocaine. Given the role of the mPFC in the regulation of the induction of behavioral sensitization, we hypothesize that the normalization of DA neurotransmission in the
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