title: Importance of D1 and D2 receptor stimulation for the induction and expression of cocaine-induced behavioral sensitization in preweanling rats.
abstract: The behavioral manifestations of psychostimulant-induced sensitization vary markedly between young and adult rats, suggesting that the neural mechanisms mediating this phenomenon differ across ontogeny. In this project we examined the importance of D1 and D2 receptors for the induction and expression of cocaine-induced behavioral sensitization during the preweanling period. In the behavioral experiments, rats were injected with reversible D1 and/or D2 antagonists (SCH23390 and/or raclopride) or an irreversible receptor antagonist (EEDQ) either before cocaine administration on the pretreatment day (induction) or before cocaine challenge on the test day (expression). In the EEDQ experiments, receptor specificity was assessed by using selective dopamine antagonists to protect D1 and/or D2 receptors from inactivation. Receptor binding assays showed that EEDQ caused substantial reductions in dorsal striatal D1 and D2 binding sites, while SCH23390 and raclopride fully protected D1 and D2 receptors from EEDQ-induced alkylation. Behavioral results showed that neither D1 nor D2 receptor stimulation was necessary for the induction of cocaine sensitization in preweanling rats. EEDQ disrupted the sensitization process, suggesting that another receptor type sensitive to EEDQ alkylation was necessary for the induction process. Expression of the sensitized response was prevented by an acute injection of a D1 receptor antagonist. The pattern of DA antagonist-induced effects described for preweanling rats is, with few exceptions, similar to what is observed when the same drugs are administered to adult rats. Thus, it appears that maturational changes in D1 and D2 receptor systems are not responsible for ontogenetic differences in the behavioral manifestation of cocaine sensitization.
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, USA. Electronic address: smcdouga@csusb.edu.
authors.forename: Sanders A
authors.initials: SA
authors.lastname: McDougall
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, USA.
authors.forename: Krista N
authors.initials: KN
authors.lastname: Rudberg
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Veliz
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, USA.
authors.forename: Janhavi M
authors.initials: JM
authors.lastname: Dhargalkar
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, USA.
authors.forename: Aleesha S
authors.initials: AS
authors.lastname: Garcia
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, USA.
authors.forename: Loveth C
authors.initials: LC
authors.lastname: Romero
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, USA; Neuroscience Program, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Gonzalez
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, USA.
authors.forename: Alena
authors.initials: A
authors.lastname: Mohd-Yusof
authors.affiliation: Department of Psychology, California State University, San Bernardino, CA, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Crawford
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D059333:Central Nervous System Sensitization / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D017072:Neostriatum / Q000187:drug effects*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D020891:Raclopride; C000470:EEDQ; D003042:Cocaine
keywords: Behavioral sensitization; Cocaine; EEDQ; Ontogeny; Raclopride; SCH23390