Repeated treatment with the kappa opioid receptor agonist U69593 reverses enhanced K+ induced dopamine release in the nucleus accumbens, but not the expression of locomotor sensitization in amphetamine-sensitized rats.
The effects after the acute activation of the kappa opioid receptor (KOR) can be distinguished from the effect after repeated administration of KOR agonist. Here, we report the effect of repeated administration of U69593 during abstinence after amphetamine-induced locomotor sensitization. Rats were injected once daily with amphetamine for five consecutive days. From day 6 to 9, rats that developed locomotor sensitization, received once daily injection of U69593 or vehicle. On day 10, all rats were injected with a challenging dose of amphetamine and locomotor activity was measured to assess the expression of sensitization. Microdialysis studies were carried out to assess dopamine extracellular levels in NAc. Rats that develop and express horizontal locomotor sensitization to amphetamine show increased dopamine release in the NAc induced by high K(+). The repeated treatment with U69593 reverses the sensitized depolarization-stimulated dopamine release in the NAc, but not the expression of locomotor sensitization induced by amphetamine. Thus, repeated activation of KORs during early amphetamine withdrawal dissociates the behavioral responses and the neurochemical responses that accompany the expression of sensitization to amphetamine.
Millenium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.
Angélica del Pilar
Adel P
Escobar
Francisca Alejandra
FA
Cornejo
María Estela
ME
Andrés
José Antonio
JA
Fuentealba
D000662:Amphetamines / Q000008:administration & dosage*; D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D000662:Amphetamines; D044482:Benzeneacetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C045444:U 69593; D011188:Potassium; D004298:Dopamine