title: Dopamine and endogenous opioid regulation of picrotoxin-induced locomotion in the ventral pallidum after dopamine depletion in the nucleus accumbens.
abstract: Microinjection of picrotoxin or the mu-opioid agonist, Tyr-D-Ala-Gly-NmePhe-Gly-OH (DAMGO), into the ventral pallidum (VP) produces an increase in locomotor activity that is antagonized by dopamine receptor blockade. To investigate the regulation of VP-induced locomotion by the dopaminergic innervation of the nucleus accumbens (NA) and the role of opioid receptors in this regulation, dopamine innervation of the NA was bilaterally lesioned with 6-hydroxydopamine (6-OHDA). The lesions resulted in an 89-97% depletion of tissue dopamine levels in the nucleus accumbens compared with sham-lesioned rats. Dopamine depletion in the NA failed to significantly antagonize picrotoxin or DAMGO injected into the VP. However, the dopamine receptor antagonist, haloperidol (0.1 mg/kg, IP), blocked the picrotoxin-initiated increase in horizontal photocell counts in both sham- and 6-OHDA-lesioned rats. The opioid receptor antagonist, naloxone (1.0 mg/kg, SC), also blocked the picrotoxin-induced locomotion in 6-OHDA-lesioned rats but did not block locomotion in the sham-lesioned rats. At a higher dose (3.0 mg/kg, SC), naloxone blocked picrotoxin-induced locomotion in both sham- and 6-OHDA-lesioned rats. These results indicate that although dopamine depletion in the NA does not affect the permissive role of dopamine transmission on locomotion elicited from the VP, it results in an increased sensitivity to enkephalinergic transmission.
authors.affiliation: Alcohol and Drug Abuse Program, Washington State University, Pullman 99164-6520.
authors.forename: L
authors.initials: L
authors.lastname: Churchill
authors.forename: M C
authors.initials: MC
authors.lastname: Austin
authors.forename: P W
authors.initials: PW
authors.lastname: Kalivas
mesh_terms: D000818:Animals; D004298:Dopamine / Q000494:pharmacology* / Q000502:physiology*; D004723:Endorphins / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D005917:Globus Pallidus / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013563:Sympathectomy, Chemical
chemical_list: D004298:Dopamine; D004723:Endorphins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins; D006220:Haloperidol; D009270:Naloxone; D010852:Picrotoxin