title: Altered behavioral response to dopamine D3 receptor agonists 7-OH-DPAT and PD 128907 following repetitive amphetamine administration.
abstract: Behavioral sensitization, the progressive and enduring enhancement of certain behaviors following repetitive drug use, is mediated in part by dopaminergic pathways. Increased locomotor response to drug treatment, a sensitizable behavior, is modulated by an opposing balance of dopamine receptor subtypes, with D1/D2 dopamine receptor stimulation increasing and D3 dopamine receptor activation inhibiting amphetamine-induced locomotion. We hypothesize that tolerance of D3 receptor locomotor inhibition contributes to behavioral sensitization. In order to test the hypothesis that expression of behavioral sensitization results in part from release of D3 receptor-mediated inhibition, thereby resulting in decreased response to D3 receptor agonists, we examined the effect of repetitive amphetamine administration on the behavioral response to the D3 receptor preferring agonists 7-OH-DPAT and PD 128907. D3-selective effects have recently been described for both drugs at a low dose. At 1 week following completion of a repetitive treatment regimen, amphetamine-pretreated rats displayed a decreased response to D3-selective doses of both 7-OH-DPAT and PD 128907, when compared to animals receiving saline pretreatment. Moreover, in addition to the quantitative alteration in response, there was a change in the inter-relation between response to amphetamine and D3 agonist. A highly significant inverse relation between locomotor inhibitory response to PD 128907 and the locomotor-stimulant response to amphetamine was observed prior to amphetamine treatment. In contrast, 10 days following repetitive amphetamine treatment, the relation between response to PD 128907 and amphetamine was not detected. The observed behavioral alteration could not be accounted for by changes in D3 receptor binding in ventral striatum. These findings suggest a persistent release of D3 receptor-mediated inhibitory influence contributes to the expression of behavioral sensitization to amphetamine.
authors.affiliation: Department of Psychiatry V-116A, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA. neil.richtand@uc.edu
authors.forename: Neil M
authors.initials: NM
authors.lastname: Richtand
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Welge
authors.forename: Beth
authors.initials: B
authors.lastname: Levant
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Logue
authors.forename: Scott
authors.initials: S
authors.lastname: Hayes
authors.forename: Laurel M
authors.initials: LM
authors.lastname: Pritchard
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Geracioti
authors.forename: Lique M
authors.initials: LM
authors.lastname: Coolen
authors.forename: S Paul
authors.initials: SP
authors.lastname: Berger
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010078:Oxazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000502:physiology; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D000661:Amphetamine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin