Neuroanatomical relationship between type 1 cannabinoid receptors and dopaminergic systems in the rat basal ganglia.

Dopamine and endocannabinoids are neurotransmitters known to play a role in the activity of the basal ganglia motor circuit. While a number of studies have demonstrated functional interactions between type 1 cannabinoid (CB1) receptors and dopaminergic systems, we still lack detailed neuroanatomical evidence to explain their relationship. Single- and double-labeling methods (in situ hybridization and immunohistochemistry) were employed to determine both the expression and localization of CB1 receptors and tyrosine hydroxylase (TH) in the basal ganglia. In the striatum, we found an intense signal for CB1 receptor transcripts but low signal for CB1 receptor protein, whereas in the globus pallidus and substantia nigra we found the opposite; no hybridization signal but intense immunoreactivity. Consequently, CB1 receptors are synthesized in the striatum and mostly transported to its target areas. No co-expression or co-localization of CB1 receptors and TH was found. In the caudate-putamen, globus pallidus and substantia nigra, TH-immunoreactive fibers were interwoven with the CB1 receptor-immunoreactive neuropil and fibers. Our data suggest that the majority of the striatal CB1 receptors are located presynaptically on inhibitory GABAergic terminals, in a position to modulate neurotransmitter release and influence the activity of substantia nigra dopaminergic neurons. In turn, afferent dopaminergic fibers from the substantia nigra innervate CB1 receptor-expressing striatal neurons that are known to also express dopamine receptors. In conclusion, these data provide a neuroanatomical basis to explain functional interactions between endocannabinoid and dopaminergic systems in the basal ganglia.

Hypothalamic-pituitary-adrenal function.

Basal hypothalamic-pituitary-adrenal (HPA) function is characterised by pulses of corticosterone secretion followed by a transient refractory period when the axis appears to be inhibited. In females pulses of corticosterone secretion occur approximately once per hour with variation in pulse amplitude underlying a diurnal rhythm. Males show smaller pulses of secretion which become widely spaced during the early light phase nadir. Pulsatility is altered by genetic programming, early life experiences and reproductive status. Activation of the HPA axis during adjuvant induced arthritis results in an increase in the pulse frequency. This is associated with a marked change in hypothalamic gene expression with a diminution of CRH mRNA and a marked increase of AVP mRNA which becomes the predominant HPA secretagogue.

Significance of pulsatility in the HPA axis.

A stress-free automated blood sampling system has been employed to demonstrate pulsatile hypothalamo-pituitary-adrenal (HPA) activity in the rat. In females, pulses of corticosterone secretion occur approximately once/hour throughout the 24 h cycle, with variation in pulse amplitude underlying a diurnal rhythm. Males show smaller pulses of secretion which become widely spaced during the early light phase nadir. Ageing does not affect the occurrence of pulses but the diurnal variation is lost. Analysis of the relationship between the HPA response to an acute noise stress and its coincidence with the various phases of the pulse, suggests that pulsatile activity arises from alternating periods of activation and suppression. Responses to i.v. corticotropin-releasing factor are not affected by pulse phase, indicating that this relationship is not generated at the pituitary-adrenal level. This phase relationship holds for all strains of rat except the hyperresponsive Fischer-344 in which an exaggerated stress response arises from a lack of phase-dependent suppression. Patterns of pulsatile activity are also modulated by neonatal programming or chronic HPA activation arising from adjuvant-induced arthritis, with consequent impact upon the response to acute stimuli. Thus, variations in the patterns of pulsatile activity are important determinants of both basal secretion and acute responses of the HPA axis.

The effects of subclinical fasciolosis on hepatic secretory function in sheep.

The effects of subclinical fasciolosis at various stages of its development on bile flow and bile acid secretion and on the hepatobiliary transport of bilirubin were investigated in experimentally infected sheep. Bile flow was significantly reduced by weeks 6-14 postinfection. This was accompanied by a decrease in bile acid secretion by weeks 6-8. Serum AST and GLDH activities and serum bile acid concentration were significantly elevated from weeks 6 to 14. Total serum bilirubin was maximally increased at 6 weeks postinfection and remained elevated at weeks 8 and 14. Increases corresponded to both unconjugated and conjugated fractions, although the conjugated/total bilirubin ratio was enhanced in all infected animals. Biliary bilirubin secretion declined from weeks 6 to 14. No alteration was detected in either uridine diphosphate (UDP)-glucuronosyltransferase activity, cytochrome P-450 concentration, or hematological markers of hemolysis. This study shows that the migration of immature flukes in the course of ovine fasciolosis causes a cholestatic phenomenon responsible for changes in serum and biliary bilirubin levels.