The International Journal of Neuropsychopharmacology

Research Article

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

Devon L. Grahama1, Robyn M. Amos-Kroohsa1, Amanda A. Brauna1, Curtis E. Gracea1, Tori L. Schaefera1, Matthew R. Skeltona1, Michael T. Williamsa1 and Charles V. Vorheesa1 c1

a1 Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

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.

(Received September 06 2011)

(Reviewed October 05 2011)

(Revised January 06 2012)

(Accepted January 30 2012)

(Online publication March 06 2012)

Key words

  • Development;
  • locomotor activity;
  • methamphetamine;
  • MK-801;
  • p-chloroamphetamine;
  • quinpirole;
  • quipazine;
  • SKF82958

Correspondence:

c1 Address for correspondence: C. V. Vorhees, PhD, Division of Neurology (MLC 7044), Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA. Tel.: 513 636 8622 Fax: 513 636 3912 Email: charles.vorhees@cchmc.org