title: Neonatal +-methamphetamine exposure in rats alters adult locomotor responses to dopamine D1 and D2 agonists and to a glutamate NMDA receptor antagonist, but not to serotonin agonists.
abstract: Neonatal exposure to (+)-methamphetamine (Meth) results in long-term behavioural abnormalities but its developmental mechanisms are unknown. In a series of experiments, rats were treated from post-natal days (PD) 11-20 (stage that approximates human development from the second to third trimester) with Meth or saline and assessed using locomotor activity as the readout following pharmacological challenge doses with dopamine, serotonin and glutamate agonists or antagonists during adulthood. Exposure to Meth early in life resulted in an exaggerated adult locomotor hyperactivity response to the dopamine D1 agonist SKF-82958 at multiple doses, a high dose only under-response activating effect of the D2 agonist quinpirole, and an exaggerated under-response to the activating effect of the N-methyl-d-aspartic acid (NMDA) receptor antagonist, MK-801. No change in locomotor response was seen following challenge with the 5-HT releaser p-chloroamphetamine or the 5-HT2/3 receptor agonist, quipazine. These are the first data to show that PD 11-20 Meth exposure induces long-lasting alterations to dopamine D1, D2 and glutamate NMDA receptor function and may suggest how developmental Meth exposure leads to many of its long-term adverse effects.
authors.affiliation: Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH 45229-3039, USA.
authors.forename: Devon L
authors.initials: DL
authors.lastname: Graham
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Amos-Kroohs
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Braun
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Grace
authors.forename: Tori L
authors.initials: TL
authors.lastname: Schaefer
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Skelton
authors.forename: Michael T
authors.initials: MT
authors.lastname: Williams
authors.forename: Charles V
authors.initials: CV
authors.lastname: Vorhees
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
chemical_list: D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D017366:Serotonin Receptor Agonists; D018698:Glutamic Acid; D008694:Methamphetamine; D011814:Quipazine