Altered pre- and postsynaptic dopamine receptor functions in spontaneously hypertensive rat: an animal model of attention-deficit hyperactivity disorder.
Dopamine receptor function in spontaneously hypertensive rats (SHR) and in control progenitor Wistar-Kyoto (WKY) rats was assessed from their dopamine D1-like/D2-like receptor-mediated jaw movements and dopamine release from the nucleus accumbens and from the ventrolateral striatum measured by an in vivo microdialysis technique. Spontaneous locomotor activity and rearing were significantly higher in SHR than in WKY rats. Co-administration of SKF 38393 (1.0, 2.0 and 3.0 mg/kg), a dopamine D1-like receptor agonist, and quinpirole (1.0 mg/kg), a dopamine D2-like receptor agonist, produced repetitive jaw movements in WKY rats in a dose-dependent manner. However, this synergism was not evident in SHR. Basal dopamine levels in both the nucleus accumbens and the ventrolateral striatum were lower in SHR than WKY rats, though the levels of dopamine were lower in the nucleus accumbens than the ventrolateral striatum in both strains. After infusion of quinpirole (100 microM for 180 min) the dopamine levels in both regions were reduced. In the nucleus accumbens, the quinpirole-mediated reduction of dopamine release at 40 min and 60 min after infusion was larger in SHR than WKY rats, whereas this difference between the SHR and WKY rats was small in the ventrolateral striatum. The present study therefore suggests that, when compared to WKY rats, postsynaptic dopamine D1-like/D2-like receptors in the SHR are hyposensitive, while presynaptic dopamine D2-like receptors located particularly in the nucleus accumbens are hypersensitive.
Fujita
Satoshi
S
Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, Tokyo 101-8310, Japan.
Okutsu
Hiroko
H
Yamaguchi
Haruhiko
H
Nakamura
Shin
S
Adachi
Kazunori
K
Saigusa
Tadashi
T
Koshikawa
Noriaki
N
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D003342:Corpus Striatum / Q000503:physiopathology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D008334:Mandible / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009068:Movement; D009714:Nucleus Accumbens / Q000503:physiopathology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D017661:Receptors, Presynaptic; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine