The mesolimbic nucleus accumbens is critically involved with the mediation of the motor inhibitory and facilitatory effects of dopamine agonists on mouse spontaneous climbing behaviour.
Mouse spontaneous climbing behaviour was dose-dependently inhibited by putative dopamine agonists administered subcutaneously (s.c.) or directly into the mesolimbic nucleus accumbens. ED50 values for s.c. administrations of apomorphine, bromocriptine, DPI, 3-PPP and DK118 (5-hydroxy-6-methyl-2-di-n-propylaminotetralin) were 0.01, 0.26, 0.17, 0.24 and 0.0004 mg/kg respectively, and for intra-accumbens apomorphine, DPI, bromocriptine, DK118 and 2-di-n-propylamino-5,6-dihydroxytetralin were 0.21, 0.22, 7.5, 0.00034 and 0.000034 micrograms respectively. Dose-dependent reduction in motor inhibitory potential/motor facilitation was also recorded for higher doses of apomorphine given s.c., or for apomorphine, DK118 and 2-di-n-propylamino-5,6-dihydroxytetralin given intra-accumbens (ED50 values to restore spontaneous climbing to control values were 4.1, 4.2 and 0.8 micrograms respectively). The motor inhibitory actions of apomorphine, 3-PPP, DK118 and 2-di-n-propylamino-5,6-dihydroxytetralin were antagonised by (-)-sulpiride, but not by yohimbine or prazosin. The actions of DPI were yohimbine-sensitive. Whilst the motor inhibition caused by s.c. bromocriptine was neuroleptic-sensitive, that observed on intra-accumbens injection was resistant to all antagonists. The intra-accumbens effectiveness of the dopamine agonists could not be mimicked by injections above the nucleus accumbens (into the head of the caudate-putamen complex) or below the nucleus accumbens (into the tuberculum olfactorium) (with the exception of the effectiveness of bromocriptine administered into the tuberculum olfactorium). It is suggested that the actions of 'dopamine agonist' to both inhibit and facilitate mouse spontaneous climbing behaviour involves an action in the mesolimbic nucleus accumbens. Whilst the mechanisms involved are generally neuroleptic-sensitive, alpha 2-adrenoceptor (for DPI) and other unidentified mechanisms (for bromocriptine) may also be important.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D012686:Septal Nuclei / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D013764:Tetrahydronaphthalenes; D013469:Sulpiride; C031457:DK 118; D001058:Apomorphine; D004298:Dopamine; D011224:Prazosin