SummaryThe present study examined the impact of repeated administration of a synthetic cannabinoid agonist, WIN 55,212-2 on the coeruleo-cortical pathway, a circuit implicated in anxiety. Male SpragueDawley rats received repeated systemic injections of WIN 55,212-2 (3.0 mg/kg). A separate group of rats received repeated WIN 55,212-2 injections followed by a period of abstinence. Control animals received vehicle injections. Ninety minutes following the last injection on day 8, anxietyrelated behavior was assessed using the elevated plus maze. The abstinent group was tested after another 8 days. Following behavioral testing, brain tissue was extracted from the locus coeruleus (LC) and probed for tyrosine hydroxylase (TH) expression. In a separate group of animals, in vivo microdialysis was used to monitor extracellular norepinephrine efflux in the frontal cortex following repeated WIN 55,212-2 administration and following a period of abstinence.Repeated administration of WIN 55,212-2 evoked an anxiogenic-like response that was accompanied by an increase in TH protein expression in the LC. A similar neurochemical profile was observed using in vivo microdialysis where an augmented increase in cortical norepinephrine efflux was identified in response to a systemic injection of WIN 55,212-2 on day 8. Anxiety-like behavior, catecholamine synthesizing enzyme levels and NE efflux returned to control values after eight days of abstinence.The present findings indicate that repeated administration of a synthetic cannabinoid receptor agonist induces transient anxiety-like behaviors that correlate with increases in catecholamine synthesizing enzyme expression in the LC and augmented norepinephrine efflux in response to a challenge injection of WIN 55,212-2.

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SUMMARY A population-based survey of 134 white men, recruited from the Chicago People's Gas Company labor force, was carried out to examine the association between sodium-lithium (Na-Li) countertransport and hypertension. Of the 134 participants in this industry-sponsored periodic health examination, 64 were normotensive and 70 were either taking antihypertensive medications or had a systolic pressure 3= 140 or a diastolic pressure 2= 90 mm Hg. The hypertensives were older and more overweight. Countertransport was significantly higher in hypertensives than in normotensives. Among the three subgroups of hypertensives -untreated borderline (140/90 to 160/95 mm Hg), untreated definite (over 160/95 mm Hg), and treated -an increase in countertransport was consistently observed, significant for the latter two groups. The relationship between countertransport and hypertension was independent of overweight, with countertransport being significantly related to both blood pressure and overweight. Altered ion transport may play an important role in the etiology and/or pathophysiology of hypertension. (Hypertension 5:363-367, 1983) KEY WORDS • countertransport • sodium metabolism • blood pressure R ED blood cell sodium-dependent membrane processes are currently being studied in relation to the etiology and pathogenesis of hypertension. 1 " 14 Previous case control studies have demonstrated a relationship between sodium-lithium (Na-Li) countertransport and hypertension.'-7 -15~17 This report described the results of a populationbased cross-sectional survey in employed white men relating levels of countertransport to the presence of hypertension. Methods Data CollectionVolunteers for this study were male employees (the great majority of whom were white) of the Chicago People's Gas Company participating in the companysponsored periodic health examination. The participation rate in this examination is over 90%. l8 During the period from June 1981 to December 1981, on a semi weekly basis, without selection the first four employees who presented at the company medical office for their regularly scheduled examination were invited to participate; response rate was 100%.A nurse measured blood pressure after the man had rested quietly in the sitting position for 5 minutes. Korotkoff sounds phases I and V were recorded from a single reading with a standard mercury sphygmomanometer. While blood was being sampled for routine laboratory analyses, an additional 15 cc of venous blood was collected in plastic tubes containing ammonium heparin. Samples were collected in the fasting state before 10 a.m. With the man in indoor clothes, with shoes off, height and weight were measured on a balance scale. Medical history was obtained through the use of a self-administered questionnaire.Of 157 white men participating in the study, 21 were excluded from this report because of a major illness (renal, hormonal, psychiatric) thought to influence intracellular ion metabolism. 6 l9 -2I In addition, two participants were excluded because of extremely...

1. There was a significant positive relationship between sodium-stimulated lithium efflux and systolic blood pressure (r = 0.512) in erythrocytes of black school children. Weight was also positively and significantly correlated with blood pressure. Although erythrocyte sodium concentration did not bear any significant relationship with blood pressure, it did bear significant inverse relationship with urinary sodium excretion. 2. High-school students were randomly assigned to either the experimental or the control group. In the former a reduction of about 70% in salt intake was achieved. After 24 days, the erythrocyte sodium concentration was significantly reduced in the experimental group. A non-significant decline in systolic blood pressure was observed in the experimental group; no change was detectable in the control group for either erythrocyte sodium concentration or systolic blood pressure.