Ontogeny of dopamine agonist-induced sensitization: role of NMDA receptors (original) (raw)

Abstract

In contrast to adults, preweanling rats exhibit behavioral sensitization for only a few days after cessation of dopamine (DA) agonist treatment. The reasons for this ontogenetic difference are uncertain, but maturational changes in the _N_-methyl-d-aspartate (NMDA) receptor may be responsible, since stimulation of these receptors is necessary for the development of DA agonist-induced sensitization in adult rats. The purpose of the present study was to examine the relationship between NMDA receptor functioning and DA agonist-induced sensitization during the preweanling period. To that end, 17-day-old rats were injected (IP) on 4 consecutive days with saline or 0.3 mg/kg dizocilpine (a non-competitive NMDA receptor antagonist) followed, 30 min later, by an injection of saline, 2.5 mg/kg amphetamine (an indirect DA agonist), or 1.0 mg/kg NPA (a direct DA agonist). Sensitization was tested 2 days later (i.e., at 22 days of age), with rats receiving a challenge injection of saline, amphetamine, NPA, or dizocilpine. Results showed that the NMDA antagonist had adult-like effects on the behavioral sensitization of preweanling rats, as amphetamine-and NPA-induced sensitization were eliminated by dizocilpine pretreatment. When given alone, dizocilpine substantially increased the locomotor activity (i.e., line-crosses) of preweanling rats, an effect that became sensitized with repeated drug treatment. Lastly, preweanling rats already sensitized to dizocilpine did not exhibit cross-sensitization to amphetamine or NPA. Thus, with few exceptions, NMDA receptor stimulation appears to modulate sensitization in a similar fashion across ontogeny. This finding suggests that maturational differences in the NMDA receptor system are not responsible for the lack of long-term sensitization in the younger animal.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Author information

Authors and Affiliations

  1. Department of Psychology, California State University, San Bernardino, CA 92407, USA, , , , , , US
    M. A. Duke, Jason O’Neal & S. A. McDougall

Authors

  1. M. A. Duke
  2. Jason O’Neal
  3. S. A. McDougall

Additional information

Received: 9 April 1996 / Final version: 4 September 1996

Rights and permissions

About this article

Cite this article

Duke, M., O’Neal, J. & McDougall, S. Ontogeny of dopamine agonist-induced sensitization: role of NMDA receptors.Psychopharmacology 129, 153–160 (1997). https://doi.org/10.1007/s002130050175

Download citation