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Additional file 1. No memory deficits in 9-months-old TgAD rats.

Additional file 2. Fullblot images.

Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

We studied the effects of chloramphenicol on brain glucose utilization and sleep-wake cycles in rat. After slightly anaesthetized animals were injected with [18F]fluoro-2-deoxy-D-glucose, we acquired time-concentration curves from three radiosensitive beta microprobes inserted into the right and left frontal cortices and the cerebellum, and applied a three-compartment model to calculate the cerebral metabolic rates for glucose. The sleep-wake cycle architecture was analysed in anaesthetic-free rats by recording electroencephalographic and electromyographic signals. Although chloramphenicol is a well-established inhibitor of oxidative phosphorylation, no compensatory increase in glucose utilization was detected in frontal cortex. Instead, chloramphenicol induced a significant 23% decrease in the regional cerebral metabolic rate for glucose. Such a metabolic response indicates a potential mismatch between energy supply and neuronal activity induced by chloramphenicol administration. Regarding sleep-wake states, chloramphenicol treatment was followed by a 64% increase in waking, a 20% decrease in slow-wave sleep, and a marked 59% loss in paradoxical sleep. Spectral analysis of the electroencephalogram indicates that chloramphenicol induces long-lasting modifications of delta-band power during slow-wave sleep.

A new beta-microprobe (betaP) has been used to locally measure the time-concentration curve of a radiolabeled substance. The betaP, analogous to positron emission tomography methodology, is useful for in vivo animal studies because it can acquire time-concentration curves with high temporal and spatial resolution. Using [18F]fluoro-2-deoxy-D-glucose and betaP, we evaluated the reliability of the biologic parameters and we compared this method with the [14C]2-deoxy-D-glucose autoradiography. BetaP time-concentration curves in three regions of the brain were obtained from 24 rats. Four kinetic parameters (K1-k4) were estimated from 60-minute experimental periods using a three-compartment model. Best fits were obtained when the vascular fraction (Fv) was estimated simultaneously with the four kinetic parameters (K1-k4). The mean estimated Fv values were about 5.5% for the frontal cortex regions and 8.0% for the cerebellum. Correlation coefficients higher than 0.830 were observed between regional cerebral metabolic rates for glucose (rCMRglc) values obtained by betaP and autoradiography. In addition, the betaP-derived input function was similar to that obtained by manual sampling. Our findings show that reliable rCMRglc values can be obtained using betaP.