Stimulation of cortical acetylcholine efflux by FG 7142 measured with repeated microdialysis sampling

Abstract

The effects of the benzodiazepine receptor partial inverse agonist beta-carboline FG 7142 on cortical ACh efflux were determined using in vivo microdialysis in freely-moving rats. Additionally, a within-subjects, repeated-dialysis experimental design (four microdialysis sessions; removable dialysis probe) was evaluated as a method for measuring changes in basal and FG 7142-stimulated ACh efflux in the frontoparietal cortex. FG 7142 (4.0, 8.0, and 16.0 mg/kg) produced a 150-470% increase in cortical ACh efflux, with a dose-dependent effect on the duration of the increase in efflux. Basal cortical ACh efflux was lower in session 4 than in session 1. However, the ability of FG 7142 to stimulate efflux was unchanged by repeated dialysis testing. The ability of tetrodotoxin (1.0 microM) to suppress both basal and FG 7142-stimulated ACh efflux was also unaffected by repeated dialysis testing. These results demonstrate that systemically administered benzodiazepine receptor inverse agonists stimulate cortical ACh efflux, and that repeated-measures experimental designs can be valid for determining certain changes in cortical ACh efflux with in vivo microdialysis.

Dopamine D3 receptor antagonists improve the learning performance in memory-impaired rats

“…The behavioural effects of FG-7142 seem to be very complex in nature, involving activation of cholinergic (Sarter et al 2001), glutamatergic (Karreman and Moghaddam 1996) and noradrenergic (Birnbaum et al 1999) systems. For example, Moore et al (1995) found that the compound strongly elevated the cortical acetylcholine efflux, which-according to the hypothesis of Sarter et al (2001)-induces a hyperattentional state leading to impairment in cognitive/cortical processing, a defect seen in schizophrenics as well. However, Murphy et al (1996a,b) demonstrated that FG-7142 induced an increase of dopamine release in the prefrontal cortex.…”

Differential neurochemical and behavioral adaptation to cocaine after response contingent and noncontingent exposure in the rat

“…We have utilized this method in a recently published study (Lecca et al 2006a,b). As pointed out in that study (Lecca et al 2006a), daily probe insertion has been already utilized by Fumero et al (1994), Georgieva et al (1993), Moore et al (1995), andMartin-Fardon et al (1997), who regarded it as a valid means for chronically monitoring in vivo DA transmission. Unsatisfactory results were reported by Camp and Robinson (1992) and Robinson and Camp (1991), who reinserted the probe after 1 week of permanence in situ.…”

Direct Examination of Local Regulation of Membrane Activity in Striatal and Prefrontal Cortical Neurons in Vivo Using Simultaneous Intracellular Recording and Microdialysis

“…Although previous studies have explored the impact of microdialysis procedures on the regulation of neurotransmitter efflux (DeBeor and Abercrombie, 1996; cf. Moore et al, 1996) and used reverse microdialysis or micropipette infusions to deliver drugs locally near an intracellular recording electrode (Paré et al, 1998a,b;Castro-Alamancos, 2000), the present study is the first to examine the impact of microdialysis on the membrane activity of neurons in the vicinity of the probe. If the probe implantation or dialysis procedure had severely disrupted synaptic activity either mechanically or by altering the diffusion of locally released neurotransmitters, it is likely that significant differences in natural membrane activity, input resistance, and spike characteristics of neurons recorded proximal to the probe would have been observed compared with intact controls (Wilson, 1993;O'Donnell and Grace, 1995).…”