Localized and discrete changes in neuropeptide (LHRH and TRH) and neurotransmitter (NE and DA) concentrations within the olfactory bulbs of male mice as a function of social interaction

Individually housed male mice were exposed to either an intact male or an ovariectomized female mouse for 1 min and decapitated at 5, 15, or 60 min to examine the hypothesis whether discrete changes in olfactory bulb neuropeptide (LHRH and TRH) and neurotransmitter (NE and DA) concentrations would occur following onset of exposure. A nonexposed control group (decapitated at time 0) was also included. Bilateral olfactory bulbs were dissected into anterior dorsal (ADOB) and posterior dorsal (PDOB) olfactory bulb fragments and prepared for radioimmunoassays (LHRH and TRH) or radioenzymatic assays (NE and DA). Concentrations of LHRH and NE, but not of TRH and DA, from the PDOB were significantly greater than those of ADOB fragments. Exposure to a male resulted in a significant increase of PDOB LHRH at 5 min following exposure and a significant increase in LHRH at 15 min following female exposure. Norepinephrine within the ADOB and PDOB and DA within the PDOB demonstrated a statistically significant increase at 60 min following exposure to an ovariectomized female. In marked contrast, no statistically significant changes were obtained following male exposure. These results not only demonstrate a preferential localization of neuroregulators within the olfactory bulb of male mice but discrete changes in the concentration of these neuroregulators in response to male or female exposure, suggesting the possibility that some processing and coding of chemical cue information during social encounters already occurs at the level of the olfactory bulb.     

Parity decreases methamphetamine-induced striatal dopaminergic perturbation

The role of parity upon methamphetamine-induced neurotoxicity of the striatal dopaminergic system was assessed. Female CD-1 mice either remained nulliparous or underwent one or three complete pregnancies and were designated as the 0, 1 or 3 pregnancy groups. The mice were then treated with a neurotoxic regimen of methamphetamine (MA - 40 mg/kg) or its saline vehicle (control) and striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured at 7-days post-MA. Basal levels of striatal DA, DOPAC and the DOPAC/DA ratio were similar among the saline (control) 0, 1 and 3 pregnancy groups. In response to MA, striatal DA and DOPAC were significantly decreased in the 0 and 1 pregnancy as compared with the control group. Mice with 3 pregnancies showed DA and DOPAC levels that did not differ from controls and were significantly greater than the 0 pregnancy group. The DOPAC/DA ratios of the 0 pregnancy group were significantly greater than all other groups (control, 1 and 3 pregnancy) which failed to differ among each other. These results demonstrate that parity decreases MA-induced striatal dopaminergic neurotoxicity, and the degree of this neuroprotection is related to the number of pregnancies experienced.     

The effect of hormonal condition on dose-dependent amphetamine-stimulated behaviors in the male rat

The effects of varying doses (1.25, 2.5, and 5.0 mg/kg, ip) of D-amphetamine sulfate (AMPH) on eight individual behaviors (Rearing, Grooming, Sniffing, Stationary, Gnawing, Head Bobbing, "Sleeping," and Licking) of Castrate + Oil-treated, Castrate + Testosterone Propionate (TP)-treated, and Intact male rats were examined. For Stationary, Sniffing, and "Sleeping" at 1.25 mg/kg AMPH and Rearing and Sniffing at the 2.5 mg/kg dose a significantly greater duration in the behavioral score was obtained for Castrate + Oil versus Castrate + TP and Intact males. These results indicate the complexity of the AMPH dose-response effects upon measurable behaviors, the alteration in the duration of these effects as a function of the hormonal condition of the male rat, and the importance of examining discrete components of behavior when hormone-amphetamine interactions are examined.     

Daily changes in in vitro spontaneous dopamine efflux from the corpus striatum of male rats

In the present experiment we examined the spontaneous in vitro dopamine (DA) efflux from superfused corpus striatum (CS) of male rats at 3-hr intervals throughout a 24-hr photoperiod (lights on 0500-1900 hr). Maximal mean efflux, and post-superfusion DA concentrations were obtained at 0600 hr. With the exception of 0600 hr, mean efflux was lower during the light compared to the dark phase. Interestingly, the direction of the efflux profiles also varied as a function of time demonstrating increasing, decreasing and relatively stable profiles over the superfusion period. These changes in overall mean efflux, post-superfusion tissue concentration and efflux rate profile direction indicate that circadian processes play a complex role upon the synthesis/release process of DA from the nigrostriatal dopaminergic system that is revealed under the dynamic conditions of in vitro superfusion of isolated CS fragments.     

Structure-activity relationship and docking studies of thiazolidinedione-type compounds with monoamine oxidase B

The neuroprotective activity of pioglitazone and rosiglitazone in the MPTP parkinsonian mouse prompted us to evaluate a set of thiazolidinedione (TZD) type compounds for monoamine oxidase A and B inhibition activity. These compounds were able to inhibit MAO-B over several log units of magnitude (82 nM to 600 μM). Initial structure-activity relationship studies identified key areas to modify the aromatic substituted TZD compounds. Primarily, substitutions on the aromatic group and the TZD nitrogen were key areas where activity was enhanced within this group of compounds.