These data are shown in Figure ?Figure77. Open in a separate window Fig. 1990; Imperato et al., 1993). Thus, indirect dopamine agonists such as amphetamine have been observed to produce an increase, a decrease, or no net switch in striatal ACh efflux depending on the dose administered and according to the methods used in the experiment (Ladinsky et Arbutin (Uva, p-Arbutin) al., 1975; Damsma et al., 1991; DeBoer and Abercrombie, 1996a). Such variability in ACh response to mixed dopaminergic agonists presumably displays the fact that D2-mediated inhibition or D1-mediated excitation may predominate in determining the level of RAD51A ACh output in any given circumstance and that the effects of the two influences may even cancel. It generally is usually accepted that this dopamine D2 receptor directly inhibits striatal ACh efflux via receptors located on the striatal cholinergic cells (Lehmann and Langer, 1983; DeBoer and Abercrombie, 1996b). However, the precise nature of the mechanism(s) underlying the D1-mediated activation of striatal ACh output is usually a topic of some controversy. Particularly unclear is the extent to which D1 receptors within the striatum versus extrastriatal D1 receptors contribute to this phenomenon. Although virtually all striatal cholinergic interneurons express D2 receptor mRNA in high large quantity, only a portion of these cells are reported to express low levels of D1receptor mRNA (Le Moine et al., 1990, 1991; Weiner et al., 1991). Studies of ACh release using striatal slice preparations are primarily unfavorable or equivocal, generally reporting no detectable D1 receptor-mediated modulation of ACh output in this situation (Scatton, 1982; Consolo et al., 1987; Dolezal et al., 1992; Tedford et al., 1992). These results suggest an extrastriatal mechanism of D1 receptor regulation of striatal ACh output. On the other hand, a number of microdialysis studies have reported that the application of D1 receptor-selective compounds Arbutin (Uva, p-Arbutin) into the striatum can reproduce the effects of systemic administration of such Arbutin (Uva, p-Arbutin) compounds on striatal ACh, suggesting an intrastriatal site of action (Ajima et al., 1990; Consolo et al., 1992;Anderson et al., 1994a). This latter conclusion is not definitive, however, because failure to replicate these Adult male Sprague Dawley rats (Zivic-Miller Laboratories, Pittsburgh, PA) were used. Before microdialysis probe implantation, the rats were housed individually in plastic shoe box cages under conditions of constant heat (21C) and humidity (40%) on a 12 hr light/dark cycle (lights on at 7:00 A.M. and off at 7:00 P.M.) with food and water available Injection of artificial CSF (aCSF) vehicle orSeven to 10 d before striatal microdialysis probe implantation, a unilateral guideline cannula aimed at the substantia nigra pars reticulata was implanted under chloral hydrate anesthesia (400 mg/kg, i.p.) using stereotaxic technique. Briefly, a burr hole was drilled into the skull, and a stainless steel guideline cannula (26 ga; Plastics One Inc., Roanoke, VA) was inserted to a position 0.5 mm above the substantia nigra pars reticulata at the following coordinates: anteroposterior, ?5.3 mm, and mediolateral, 2.2 mm, from bregma; and dorsoventral, ?6.7 mm, from dura (Paxinos and Watson, 1997). The guideline cannula was secured in place using skull screws and fast-curing dental cement. A dummy cannula (30 ga), which extended 0.5 mm beyond the lead cannula, was inserted. Beginning on the first day after surgery, the rats were softly dealt with twice daily to habituate them to the intracerebral injection procedures. The microdialysis probes used in the present investigation were of a vertical, concentric design and incorporated a dialysis membrane with an active length of 2 mm (outer diameter, 250 m; Spectra/Por; Spectrum, Houston, TX). A piece of PE-20 tubing (Clay Adams) served as the probe inlet, whereas a piece of fused silica capillary tubing (inner diameter, 75 m; outer diameter, 150 m; Polymicro Technologies, Phoenix, AZ) served as the store (DeBoer and Abercrombie, 1996a). Microdialysis probes were constantly perfused with aCSF (in mm: NaCl 147, KCl 2.5, CaCl2 1.3, and MgCl2 0.9, pH = 7.4) at a rate of 1 1.5 l/min by means Arbutin (Uva, p-Arbutin) of a microliter syringe pump (Harvard Apparatus). The animals were anesthetized with chloral hydrate (400 mg/kg), and a microdialysis probe was implanted into the striatum at the following coordinates (smooth skull): anteroposterior, +1.0 mm, and mediolateral, +2.7 mm, relative to bregma; and ?6.0 mm below the dura, according to.