Title

The effects of D1 receptor manipulation in the substantia nigra pars reticulata: A behavioral and neurochemical analysis

Date of Completion

January 2000

Keywords

Biology, Neuroscience|Psychology, Psychobiology

Degree

Ph.D.

Abstract

A series of fifteen experiments (Chapters 1–6 below) were conducted to investigate the effects of D1 receptor manipulation in the substantia nigra pars reticulata (SNr) on GABA levels and behavioral activity. In Chapters 1 and 2 the effects of local D1 receptor blockade in the nucleus accumbens (NA), ventrolateral neostriatum (VLS) and SNr on behavioral activity were examined. In Chapter 1 it was found that local injections of the D1 antagonist SCH 23390 produced a dose-dependent suppression of operant responding on a fixed ratio 5 (FR5) schedule, and that this effect was most potent in the SNr. In Chapter 2 the effects of local injection of SCH 23390 on locomotor activity were assessed. It was found that SCH 23390 produced a significant dose-dependent suppression of locomotion when injected into either the NA, VLS or SNr, and that this effect was approximately equipotent in these sites. In Chapters 3–6 the behavioral and neurochemical effects of D1 stimulation in the SNr were examined. In Chapter 3 it was found that local injections of the D1 agonist APB into the SNr significantly increased locomotor activity. In Chapter 4 a novel method for quantifying GABA levels in the SNr using high performance liquid chromatography (HPLC) is presented. In Chapter 5 the method developed in Chapter 4 was used to assess the effects of D1 stimulation on GABA levels in the SNr. It was found that administration of the D1 agonist APB into the SNr significantly increased GABA levels, and that this effect was blocked by co-administration of the D1 antagonist SCH 23390. In Chapter 6 the effects of direct stimulation of GABA receptors in the SNr on behavioral activities were assessed. It was found that the GABA agonist muscimol significantly increased locomotor activation, while the GABA antagonist bicuculline decreased it. Together, Chapters 1–6 suggest that the SNr is an important site at which drugs acting on D1 receptors can produce behavioral effects, and that stimulation of D1 receptors in SNr produces behavioral effects that are mediated via GABA-ergic mechanisms. ^