Acute effects of 3,4-methylenedioxymethamphetamine on striatal single-unit activity and behavior in freely moving rats: differential involvement of dopamine D(1) and D(2) receptors.
3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused amphetamine derivative that increases dopamine (DA) and serotonin release via a reverse transport mechanism. Changes in the activity of striatal neurons in response to increased DA transmission may shape the behavioral patterns associated with amphetamine-like stimulants. To determine how the striatum participates in MDMA-induced locomotor activation, we recorded the activity of >100 single units in the striatum of freely moving rats in response to a dose that increased motor activation (5.0 mg/kg). MDMA had a predominantly excitatory effect on neuronal activity that was positively correlated with the magnitude of locomotor activation. Categorizing neurons according to baseline locomotor responsiveness revealed that MDMA excited significantly more neurons showing movement-related increases in activity compared to units that were non-movement-related or associated with movement-related decreases in activity. Further analysis revealed that the drug-induced striatal activation was not simply secondary to the behavioral change, indicating a primary action of MDMA on striatal motor circuits. Prior administration of SCH-23390 (0.2 mg/kg), a D(1) antagonist, resulted in a late onset of MDMA-induced locomotion, which correlated positively with delayed neuronal excitations. Conversely, prior administration of eticlopride (0.2 mg/kg), a D(2) antagonist, completely abolished MDMA-induced locomotion, which paralleled its blockade of MDMA-induced excitatory neuronal responses. Our results highlight the importance of striatal neuronal activity in shaping the behavioral response to MDMA, and suggest that DA D(1) and D(2) receptors have distinct functional roles in the expression of MDMA-induced striatal and locomotor activation.
Ball
Kevin T
KT
Department of Psychology and Program in Neural Science, Psychology Building, Indiana University, 1101 East 10th Street, Bloomington, IN 47405-7007, USA.
Budreau
Daniel
D
Rebec
George V
GV
D000200:Action Potentials / Q000187:drug effects; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D004594:Electrophysiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology; D013997:Time Factors
D018759:Adrenergic Uptake Inhibitors; D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C045989:eticlopride; D018817:N-Methyl-3,4-methylenedioxyamphetamine