Ontogeny of dopamine agonist-induced sensitization: role of NMDA receptors.
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 (i.p.) 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.
Duke
M A
MA
Department of Psychology, California State University, San Bernardino 92407, USA.
O'Neal
J
J
McDougall
S A
SA
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000833:Animals, Suckling; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology
D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C009074:N-n-propylnorapomorphine; D016291:Dizocilpine Maleate; D000661:Amphetamine; D001058:Apomorphine