title: Morphine, cocaine and antidepressant induced motivational activity and midbrain dopaminergic neurotransmission.
abstract: Positive motivational properties of opioids, stimulants and serotonin selective reuptake inhibitors have been reported following place preference conditioning. The possibility that these effects are associated with changes in dopamine concentration in the nucleus accumbens or striatum was investigated. Male Wistar rats were place conditioned in a three compartment model to vehicle or drug (morphine 2.5 mg/kg, cocaine 5 mg/kg, sertraline 5 mg/kg or paroxetine 15 mg/kg) alternately for 8 days using a 30 min pre-treatment time. Control animals received saline only. Nucleus accumbens and striatal tissue were dissected 72 h after final drug dose, and the concentration of dopamine and its metabolites determined using high performance liquid chromatography (HPLC). Striatal dopamine D1-like receptor density was also determined through radioligand binding. Significant place preference (P<0.05) was observed with morphine, cocaine and sertraline. Morphine treated subjects showed a significant decrease (P<0.05) in striatal dopamine concentration, whilst cocaine and sertraline treatment resulted in a significant increase in striatal dopamine levels. Nucleus accumbens concentrations of dopamine, and striatal dopamine D1-like receptor density remained unchanged. The changes in striatal dopamine concentrations are consistent with withdrawal from opioid and stimulant compounds, and suggest that place preference conditioning may, in part, result from negative motivational or aversive effects.
authors.affiliation: Pharmacology Department, Welsh School of Pharmacy, Redwood Building, King Edward VII Avenue, CF10 3XF, Cardiff, UK.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Deslandes
authors.forename: David M
authors.initials: DM
authors.lastname: Pache
authors.forename: Paul
authors.initials: P
authors.lastname: Buckland
authors.forename: Robert D E
authors.initials: RD
authors.lastname: Sewell
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D009042:Motivation; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017374:Paroxetine / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D000697:Central Nervous System Stimulants; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid; D009020:Morphine; D017374:Paroxetine; D017447:Receptors, Dopamine D1; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline