Unconditional hyperactivity and transient reinforcing effects of NMDA administration into the ventral tegmental area in rats.
BACKGROUND
The dopaminergic projection from the ventral tegmental area (VTA) to the nucleus accumbens plays an important role in positive reinforcement and locomotion. Intra-VTA administration of many drugs capable of activating these neurons has been shown to be reinforcing and induce locomotion. Administration of the excitatory amino acid NMDA (N-methyl-D-aspartate) into the VTA may likewise be positively reinforcing, because it stimulates the meso-accumbens dopamine system and locomotion.


OBJECTIVE
Locomotor-rearing experiments were conducted to pinpoint the range of NMDA concentrations that induce significant locomotion and rearing, and to determine whether co-administration of the glycine binding site agonist d-serine would enhance the effects of NMDA administration into the VTA. Reinforcing effects of NMDA were assessed by intracranial self-administration procedures: a lever-press delivered a 75-nl infusion containing NMDA (0.1, 0.3 or 1.0 mM) plus serine into the VTA or an adjacent region, the supramammillary nucleus.


RESULTS
Co-administration of serine slightly enhanced rearing induced by NMDA administration. Administration of NMDA at concentrations of 0.3 or 1.0 mM (500 nl) induced vigorous locomotion and rearing. NMDA (0.3 mM) was self-administered into the VTA slightly more than vehicle in the first or second sessions, yet this small reinforcing effect became irregular in subsequent sessions. The rats did not learn to self-administer NMDA into the supramammillary nucleus.


CONCLUSIONS
Ventral tegmental NMDA injections, in the concentration range that induced marked unconditional hyperactivity, supported only marginal and transient self-administration.
Ikemoto
Satoshi
S
Behavioral Neuroscience Branch, National Institute on Drug Abuse, Department of Health and Human Services, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. sikemoto@intra.nida.nih.gov
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000139:chemically induced*; D007276:Injections, Intraventricular; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D016202:N-Methylaspartate