s of the BAP/EBPS International Workshop on The Behavioural Pharmacology of Anxiety and Depression, Bath, UK, November 20-23: PDF Only

Previous work in our laboratory has shown that Urocortin (Ucn), a peptide related to corticotropin releasing factor (CRF), injected into the basolateral nucleus of the amygdala (BLA) in male Wistar rats would result in an anxiogenic response as measured in the social interaction (SI) test. In addition, it was found that repeated injections of subthreshold doses of Ucn would ‘prime’ the animal’s response. This ‘priming’ effect induces a sensitivity to sodium lactate infusions that results in a panic-like reaction. Currently, we examined the effects of the CRF1 and CRF2 antagonist Astressin (Asn) on the anxiety-like responses produced during ‘priming’ as well as during a sodium lactate infusion into ‘primed’ rats. The results showed that Asn (60 pmoles) was able to reverse the anxiogenic effects seen during acute administration of Ucn, but was only able to partially antagonize the same response following ‘priming’ with Ucn. Furthermore, Asn administered either alone or prior to a sodium lactate infusion had no effect on the primed rat’s behavior. Autoradiographic studies, in Ucn primed and sham-primed animals indicated no significant changes in [125I]-Sauvagine binding to CRF1 and CRF2 receptors in several brain regions. Thus, a 60 pmole dose of Asn blocks the effects of an acute injection of Ucn (100 pmoles), while only partially blocking the behavioral effects after repeated injections of subthreshold doses of Ucn (6 pmoles) are given. Furthermore, Asn has no effect on anxiogenic responses due to sodium lactate infusions in ‘primed’ rats

PIOT, O; DOBLE, A; HEUILLET, E; PETITET, F; REIBAUD, M; BETSCHART, J; PAUCHET, C; OBINU, M C; MALLERON, J L; MIGNANI, S; IMPERATO, A Author Information

Healthcare providers who work with adolescents with diabetes are in an ideal position to provide education and support regarding contraceptive issues. Diabetes educators and other health professionals who counsel teens focus on other aspects of diabetes care and management but frequently do not address sexual issues or assess contraceptive practices. The purpose of this paper is to review oral contraceptive issues for teens with diabetes and to provide practice implications for health professionals who are in a favorable position to influence the quality of diabetes and general health care for these adolescents.

The NK, tachykinin receptor agonists, septide, [Sar9, Met(O2)11]SP and [Pro9]SP produced locomotor hyperactivity (10–20 min) when injected intracerebroventricularly (i.c.v.) in the guinea‐pig. Producedlocomotor The most potent in eliciting this hyperactivity was septide (from 0.63 to 5 μg), compared to [Sar9, Met(O2)11]SP, which was active at 2.5 and 5 μg and [Pro9]SP which induced a non‐significant increase even at 10 μg. Wet‐dog shakes were elicited by septide, [Sar9, Met(O2)11]SP and [Pro9]SP injected by the i.c.v. route in the guinea‐pig. [Sar9, Met(O2)11]SP, active from 0.16 to 2.5 μg was more potent than septide (active at 1.25 μg) and [Pro9]SP (active at 0.63 μg) in eliciting such behaviour. To a lesser extent, grooming was also observed after injection of these agonists. The NK2 tachykinin receptor agonist, [Lys5, MeLeu9, Nle10]NKA(4–10), up to the dose of 10 μg i.c.v. had no effect in the guinea‐pig. It neither modified locomotor activity nor induced a characteristic behavioural response. At higher doses (20μg), some toxic effects were noted. The NK3 tachykinin receptor agonist, senktide, contrasts with the NK1 receptor agonists in that it elicited only wet‐dog shakes, at doses ranging from 0.32 to 1.25 μg. It neither modified locomotor activity (1 pg) nor induced grooming (up to 5 μg) in the guinea‐pig. To our knowledge, these results are the first demonstration that the guinea‐pig could be useful to differentiate tachykinin agonists on the basis of their behavioural profile, distinct from those obtained in mice and rats.

OBJECTIVE To determine the proportion of adults with diabetesin the U.S. who have received diabetes patient education and to assess factors that determine whether patients receive this education. RESEARCH DESIGN AND METHODS A questionnaire on diabetes was administered to a representative sample of 2,405 diabetic individual≥18 years of age in the U.S. population. The questionnaire inquired about whether these individuals had ever attended a diabetes education class or program. Sociodemographic and clinical factors that may influence participation in patient education were also determined. RESULTS Of all people with diabetes, 35.1% had attended a class or program about diabetes at some time during the course of their disease,including 58.6% of individuals with insulin-dependent diabetes mellitus, 48.9% of insulin-treated individuals with non-insulin-dependent diabetes mellitus (NIDDM), and 23.7% of NIDDM individuals not treated with insulin. Younger age, black race, residence in the midwest region of the U.S., higher level of education, and presence of diabetes complications were consistentlyassociated with having had diabetes education for people with NIDDM. Although increasing income was associated with patient education for NIDDM individuals not treated with insulin, it was not an independent determinant for insulin-treated NIDDM individuals. NIDDM individuals not treated with insulin who lived alone were more likely to have had patient education than those who did not live alone. Not having a diabetes physician or not visiting onein the past year was associated with a higher likelihood of patient education for non-insulin-treated NIDDM individuals. CONCLUSIONS A large proportion of patients with diabetes has never received , diabetes education. Patient education has been recognized for its contributions to reducing the morbidity and mortality of diabetes. Consequently, special attention should be directed to the subgroups of individuals, such as those not taking insulin, those with lower socioeconomic status, and those living outside urban areas, in which the frequency of diabetes patient education is particularly low.

Potent and selective NK-1 and NK-2 agonists as well as compounds with lower selectivity and affinity for NK-1 binding sites were compared in their ability to produce scratching and grooming behaviours when injected intracerebroventricularly in mice. Septide, an agonist with a low affinity for NK-1 binding sites, [Sar9, Met(O2)11]SP and to a lesser extent [Pro9]SP, two potent and selective NK-1 agonists were the most effective drugs in stimulating these behaviours. Only high doses of [Apa9,10]SP and [Lys5, Tyr7, Pro8]NKA(4–10), two agonists with low affinity for NK-1 binding sites, produced scratching and grooming responses. Similarly, only high doses of [Lys5, MeLeu9, NLe10]NKA(4–10), a potent NK-2 agonist, produced grooming behaviour. When coinjected with the endopeptidase enzyme inhibitor phosphoramidon, the effects of [Apa9,10]SP, [Lys5, Tyr7, Pro8]NKA(4–10) and [Pro9]SP were markedly enhanced. Analyses of the potency of the different agents to displace 3H-SP binding in mouse subcortical structures revealed that the affinities of the agonists for NK-1 receptors are similar to those previously reported in rat brain. The efficacy of the agonists at producing behavioural responses was not equivalent to their potency to bind to central NK-1 receptors. These findings therefore suggest that a stimulation of NK-1 but also non classical NK-1 receptors are involved in the induction of scratching and grooming behaviours.

IDDM in children and adolescents requires that complex daily management skills be learned by children and their families. Insulin administration, nutrition therapy, and daily monitoring place the burden of self-management on parents and children, who already may be stressed. The unrelenting care required to observe and treat young children produces anxiety in parents whose children are potentially poised between hypoglycemia and DKA. Health care professionals must understand the dynamic nature of childhood diabetes and not underestimate the impact on specific developmental levels or the amount of support and education required.

1. RP 62203 (2-[3-(4-(4-fluorophenyl)-piperazinyl)propyl]naphto[1,8- ca]isothiazole-1,1-dioxide) is a novel naphtosultam derivative which shows very high affinity for 5-HT2 receptors in the rat cerebral cortex (Ki = 50.0 pM). 2. RP 62203 is relatively selective for this sub-type of 5-hydroxytryptamine (5-HT) receptor, having lower affinity for the 5-HT1A receptor and very low affinity for the 5-HT, receptor. RP 62203 displayed low to moderate affinity for alpha 1-adrenoceptors, dopamine D2 receptors and histamine H1 receptors. 3. In vivo binding experiments demonstrated that oral administration of low doses of RP 62203 led to a long-lasting (greater than 6 h) occupation of cortical 5-HT2 receptors (ID50 = 0.39 mgkg-1). 4. In cortical slices from the neonatal rat, RP 62203 potently inhibited inositol phosphate formation evoked by 5-HT, with an IC50 of 7.76 nM. 5. The activity of neurones in the raphé and their responses to microiontophoretically applied 5-HT were studied with extracellular recording electrodes in the anaesthetized rat. RP 62203 potently and dose-dependently blocked excitations evoked by 5-HT when administered at doses of 0.5-4.0 mg kg-1, i.p. In contrast, neither 5-HT-evoked depressions nor glutamate-evoked excitations of raphé neuronal firing were blocked by RP 62203 at doses as high as 8.0 mg kg-1, i.p. 6. Head twitches induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) could be abolished by low doses of RP 62203 in mice (ED50 = 0.44 mg kg-1, p.o.) and in rats (ED50 = 1.54 p.o.). Similar results were obtained with mescaline and 5-hydroxytryptophan (5-HTP). 7. The potency of RP 62203 was compared with that of three other 5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ICI 170,809. In all models, RP 62203 showed similar activity to ritanserin, whilst either ICI 169,369 or ICI 170,809 was several fold less active. 8. It is concluded that RP 62203 is a potent and selective antagonist at 5-HT2 receptors in the rodent central nervous system.

Piot, O.; Betschart, J.; Chaillou, P.; Boireau, A.; Dubedat, P.; Stutzmann, J. M.; Blanchard, J. C. Author Information

A series of 2-(aminoalkyl)naphth[1,8-cd]isothiazole 1,1-dioxides was synthesized and examined in various receptor binding tests. Most compounds demonstrated high affinity for the 5-HT2 receptor with moderate to high selectivity. A member of this series, compound 24 (RP 62203), displays high 5-HT2 receptor affinity (Ki = 0.26 nM), which is respectively more than 100 and 1000 times higher than its affinity for alpha 1 (Ki = 38 nM) and D2 (Ki greater than 1000 nM) receptors. This compound is a potent orally effective and long lasting 5-HT2 antagonist in the mescaline-induced head-twitches test in mice and rats.

In a model of physical dependence in mice, treatment with cyclopyrrolones such as zopiclone and suriclone (from 4 to 400 mg/kg/day), did not modify the sensitivity of the gamma-aminobutyric acid (GABA) receptor complex to the partial inverse agonist FG 7142 following their withdrawal, whereas sensitivity changes were observed after treatment and withdrawal from some benzodiazepines (e.g. lorazepam, diazepam, flunitrazepam and triazolam). These data suggest that, in contrast to some benzodiazepines, zopiclone and suriclone may not produce physical dependence.

A new combination reflectance meter/visually interpretable system (Glucometer II®/Glucostix®, Ames Division, Miles Laboratories, Elkhart, IN) has been designed for self blood glucose monitoring. Performance evaluation of this system demonstrates a linear relationship between meter-determined blood glucose values and laboratory-determined whole blood glucose values (y = 0.95x + 2.86, r = 0.97). In addition, 95% of visually interpreted blood glucose values are within one color block of YSI comparative values. Error grid analysis, a new method for determining the clinical accuracy of patient-determined blood glucose results, demonstrated that components of this new system produce clinically accurate blood glucose results.

Parents (n =145) of 86 children with diabetes who attended an educational seminar wrote anonymous responses to questions about poor glycemic control, guilt feelings, and coping behaviors. Children from this group were similar to our clinic population in age, sex, duration of diabetes, and HbA1 levels. Results revealed a wide range of ideas about the meaning of poor control, intense feelings of guilt, and maladaptive responses. The largest number of parents had feelings of guilt relating to dietary issues. Parents of children with diabetes have stresses that frequently may go unrecognized and may require professional help to overcome.

We evaluated the long-term effects of self-monitoring of blood glucose (SMBG) on glycemic control in a large unselected group of insulin-dependent diabetic (IDD) children and adolescents (N = 282) treated at a diabetes clinic. Among those who had been taught SMBG techniques (N = 229) and reported frequency of use (N = 209), only 26% reported monitoring three or more times per day. HbA1 levels of patients who monitored their blood most frequently did not differ from those who monitored blood less frequently or those who monitored only urine. Likewise, HbA1 levels of patients who monitored with machines did not differ from Chemstrip bG users. Accuracy was assessed in a subsample of 100 randomly selected Chemstrip bG users by comparing their Chemstrip reading with a laboratory value. Fifty-eight percent of the readings were within 20% of the laboratory value. Accuracy did not relate to frequency of monitoring or to HbA1 levels. These data suggest that frequency and accuracy of SMBG are independent and that neither ensures good glycemic control.

We report a double-crossover study to assess the impact of self-monitoring of blood glucose (SMBG) on the glycemic control of children with insulin-dependent diabetes mellitus (IDDM) on a conventional therapeutic regimen. Sixteen children were assigned to one of two groups—group A, period 1 (wk 1–13): urine testing plus SMBG; period 2 (wk 14–26): urine testing only; group B, period 1: urine only; period 2: urine testing plus SMBG. Frequent telephone contact was maintained throughout to help optimize insulin dose adjustment. At the outset, the two groups were similar in age, diabetes duration, and glycosylated hemoglobin levels (10.5 ± 0.6% and 9.5 ± 0.3% in groups A and B, respectively). No significant differences could be detected between the two groups at any stage of the study. There was, however, a trend toward lower mean blood glucose (MBG) concentration in both groups toward the end of the SMBG period. No complications of SMBG were noted, but compliance was a major problem in three children. SMBG confirmed symptoms of hypoglycemia in all children, and detected asymptomatic hypoglycemia (BG ≤ 40 mg/dl) in 11. Sixty-nine percent preferred SMBG to urine testing. We conclude that SMBG is an acceptable part of routine diabetes care in children. It is associated with very few complications and helps to confirm symptomatic hypoglycemia and detect asymptomatic hypoglycemia. However, the addition of SMBG to routine diabetes care does not necessarily lead to improved metabolic control.