title: Dopaminergic agonists administered into the nucleus accumbens: effects on extracellular glutamate and on locomotor activity.
abstract: The hypothesis to be tested was that increased dopaminergic transmission induced by amphetamine in the nucleus accumbens results in increased glutamatergic neurotransmission in this brain area and that the increase in level of this neurotransmitter contributes to behavioral effects of psychostimulant drugs. Amphetamine (1 mg/kg, i. p.) increased the amount of extracellular glutamate in the accumbens, as measured by in vivo dialysis, and stimulated locomotor activity. Amphetamine (10 mM) infused into the accumbens by reverse dialysis through the probe produced a similar stimulation of locomotor activity as systemic amphetamine but a greater increase in extracellular glutamate levels. Both of these responses to amphetamine were attenuated by either the selective D1 antagonist SCH23390 or the selective D2 antagonist eticlopride. The combination of a D1 and D2 agonist, SKF38393 (20 mM) and quinpirole (50 mM), administered into the accumbens by reverse dialysis also increased extracellular glutamate and stimulated locomotor activity. Administration of a glutamate uptake inhibitor, threo-beta-hydroxy-aspartate (50 mM), increased extracellular glutamate but did not stimulate locomotor activity. Systemic administration of caffeine (15 mg/kg, i.p.) increased locomotor activity but did not increase extracellular levels of glutamate. These data suggest that activation of dopaminergic receptors in the nucleus accumbens results in stimulation of locomotor activity and in activation of glutamatergic transmission in this brain region. However, an increase in glutamate levels in the nucleus accumbens is neither sufficient nor necessary to produce a stimulation of locomotor activity.
authors.affiliation: Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dalia
authors.forename: N J
authors.initials: NJ
authors.lastname: Uretsky
authors.forename: L J
authors.initials: LJ
authors.lastname: Wallace
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D012457:Salicylamides; D019257:Quinpirole; D002110:Caffeine; D018698:Glutamic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000661:Amphetamine; D006220:Haloperidol; C045989:eticlopride