Effect of hip hemiarthroplasty dislocation on mortality after hip fracture surgery / Efecto de la luxación de la prótesis parcial de cadera en la mortalidad tras la cirugía de fractura de cadera

Introduction: Hip arthroplasty is the treatment of choice for displaced femoral neck fractures among the older population. The hip prosthesis dislocation is one of the most pointed potential complications after hip arthroplasty, but there is a lack of updated information on the effect of dislocation on the survival of older hip fracture patients so treated by hip hemiarthroplasty. We aim to evaluate the standalone effect of hip prosthesis dislocation after hip fracture hemiarthroplasty on patients’ survival outcomes. Materials and methods: We conducted a retrospective multicenter study, including 6631 femoral neck fracture patients over 65 surgically treated by hemiarthroplasty. We made follow-up cut-offs 30-days, 6 weeks, 90-days, and one year after hospital discharge determining hip dislocation rate and patients’ survival. Results: The women population represented 78.7%, and the mean age of the population was 85.2±6.7 years. Hip prosthesis dislocation incidence was 1.9% in the first 90-days after discharge, representing 91.54% of primary dislocations yearly noted. We reported statistically significant increased mortality rates of patients presenting at least one hip prosthesis dislocation event (from 16.0% to 24.6% at 90-day after discharge, and 29.5% to 44.7% at one year), and also significantly decreasing patient survival function at 90-day (p=0.016) and one-year follow-up (p<0.001). The recurrent dislocation events (26.15%) showed even higher mortality rates (up to 60.6%, p<0.001). The multivariate Cox regression model determined that prosthesis dislocation was the only significant variable (p=0.035) affecting patient survival, increasing the risk of dying before one year of follow-up by 2.7 times. Discussion: Our study stands for the standalone hip prosthesis dislocation entailing a higher risk of death after hip fracture hemiarthroplasty in the older population.(AU)

Introducción: La artroplastia de cadera es el tratamiento de elección para las fracturas desplazadas del cuello de fémur en la población de edad avanzada. La luxación de la prótesis de cadera es una de las complicaciones potenciales tras la artroplastia de cadera, pero falta información actualizada sobre el efecto de la luxación en la supervivencia de los pacientes mayores con fractura de cadera tratados mediante hemiartroplastia de cadera. Nuestro objetivo es evaluar el efecto de la luxación de la prótesis de cadera (hemiartroplastia) como factor aislado, en la función de supervivencia de los pacientes. Materiales y métodos: Realizamos un estudio multicéntrico retrospectivo, que incluyó a 6.631 pacientes mayores de 65 años con fractura de cuello de fémur tratados quirúrgicamente mediante hemiartroplastia. Se realizaron cortes de seguimiento a los 30 días, 6 semanas, 90 días y un año del alta hospitalaria, determinando la tasa de luxación de cadera y la supervivencia de los pacientes. Resultados: La población femenina representó el 78,7%, y la edad media de la población fue de 85,2±6,7 años. La incidencia de luxación de la prótesis de cadera fue del 1,9% en los primeros 90 días tras el alta, lo que representa el 91,54% de las luxaciones primarias observadas anualmente. Se registró un aumento estadísticamente significativo de las tasas de mortalidad de los pacientes que presentaban al menos un evento de luxación de la prótesis de cadera (del 16,0 al 24,6% a los 90 días del alta, y del 29,5 al 44,7% al año), y también una disminución significativa de la función de supervivencia de los pacientes a los 90 días (p=0,016) y al año de seguimiento (p<0,001). Los eventos de luxación recurrente (26,15%) mostraron tasas de mortalidad aún más altas (hasta el 60,6%, p<0,001). El modelo multivariante de regresión de Cox determinó que la luxación de la prótesis de cadera es la única variable significativa (p=0,035) que afecta a la...(AU)

[Artículo traducido] Efecto de la luxación de la prótesis parcial de cadera en la mortalidad tras la cirugía de fractura de cadera / Effect of hip hemiarthroplasty dislocation on mortality after hip fracture surgery

Introducción: La artroplastia de cadera es el tratamiento de elección para las fracturas desplazadas del cuello de fémur en la población de edad avanzada. La luxación de la prótesis de cadera es una de las complicaciones potenciales tras la artroplastia de cadera, pero falta información actualizada sobre el efecto de la luxación en la supervivencia de los pacientes mayores con fractura de cadera tratados mediante hemiartroplastia de cadera. Nuestro objetivo es evaluar el efecto de la luxación de la prótesis de cadera (hemiartroplastia) como factor aislado, en la función de supervivencia de los pacientes. Materiales y métodos: Realizamos un estudio multicéntrico retrospectivo, que incluyó a 6.631 pacientes mayores de 65 años con fractura de cuello de fémur tratados quirúrgicamente mediante hemiartroplastia. Se realizaron cortes de seguimiento a los 30 días, 6 semanas, 90 días y un año del alta hospitalaria, determinando la tasa de luxación de cadera y la supervivencia de los pacientes. Resultados: La población femenina representó el 78,7%, y la edad media de la población fue de 85,2±6,7 años. La incidencia de luxación de la prótesis de cadera fue del 1,9% en los primeros 90 días tras el alta, lo que representa el 91,54% de las luxaciones primarias observadas anualmente. Se registró un aumento estadísticamente significativo de las tasas de mortalidad de los pacientes que presentaban al menos un evento de luxación de la prótesis de cadera (del 16,0 al 24,6% a los 90 días del alta, y del 29,5 al 44,7% al año), y también una disminución significativa de la función de supervivencia de los pacientes a los 90 días (p=0,016) y al año de seguimiento (p<0,001). Los eventos de luxación recurrente (26,15%) mostraron tasas de mortalidad aún más altas (hasta el 60,6%, p<0,001). El modelo multivariante de regresión de Cox determinó que la luxación de la prótesis de cadera es la única variable significativa (p=0,035) que afecta a la...(AU)

Introduction: Hip arthroplasty is the treatment of choice for displaced femoral neck fractures among the older population. The hip prosthesis dislocation is one of the most pointed potential complications after hip arthroplasty, but there is a lack of updated information on the effect of dislocation on the survival of older hip fracture patients so treated by hip hemiarthroplasty. We aim to evaluate the standalone effect of hip prosthesis dislocation after hip fracture hemiarthroplasty on patients’ survival outcomes. Materials and methods: We conducted a retrospective multicenter study, including 6631 femoral neck fracture patients over 65 surgically treated by hemiarthroplasty. We made follow-up cut-offs 30-days, 6 weeks, 90-days, and one year after hospital discharge determining hip dislocation rate and patients’ survival. Results: The women population represented 78.7%, and the mean age of the population was 85.2±6.7 years. Hip prosthesis dislocation incidence was 1.9% in the first 90-days after discharge, representing 91.54% of primary dislocations yearly noted. We reported statistically significant increased mortality rates of patients presenting at least one hip prosthesis dislocation event (from 16.0% to 24.6% at 90-day after discharge, and 29.5% to 44.7% at one year), and also significantly decreasing patient survival function at 90-day (p=0.016) and one-year follow-up (p<0.001). The recurrent dislocation events (26.15%) showed even higher mortality rates (up to 60.6%, p<0.001). The multivariate Cox regression model determined that prosthesis dislocation was the only significant variable (p=0.035) affecting patient survival, increasing the risk of dying before one year of follow-up by 2.7 times. Discussion: Our study stands for the standalone hip prosthesis dislocation entailing a higher risk of death after hip fracture hemiarthroplasty in the older population.(AU)

Effect of hip hemiarthroplasty dislocation on mortality after hip fracture surgery. / [Artículo traducido] Efecto de la luxación de la prótesis parcial de cadera en la mortalidad tras la cirugía de fractura de cadera.

INTRODUCTION: Hip arthroplasty is the treatment of choice for displaced femoral neck fractures among the older population. The hip prosthesis dislocation is one of the most pointed potential complications after hip arthroplasty, but there is a lack of updated information on the effect of dislocation on the survival of older hip fracture patients so treated by hip hemiarthroplasty. We aim to evaluate the standalone effect of hip prosthesis dislocation after hip fracture hemiarthroplasty on patients' survival outcomes. MATERIALS AND METHODS: We conducted a retrospective multicenter study, including 6631 femoral neck fracture patients over 65 surgically treated by hemiarthroplasty. We made follow-up cut-offs 30-days, 6 weeks, 90-days, and one year after hospital discharge determining hip dislocation rate and patients' survival. RESULTS: The women population represented 78.7%, and the mean age of the population was 85.2 ± 6.7 years. Hip prosthesis dislocation incidence was 1.9% in the first 90-days after discharge, representing 91.54% of primary dislocations yearly noted. We reported statistically significant increased mortality rates of patients presenting at least one hip prosthesis dislocation event (from 16.0% to 24.6% at 90-day after discharge, and 29.5% to 44.7% at one year), and also significantly decreasing patient survival function at 90-day (P = .016) and one-year follow-up (P < .001). The recurrent dislocation events (26.15%) showed even higher mortality rates (up to 60.6%, p < .001). The multivariate Cox regression model determined that prosthesis dislocation was the only significant variable (P = .035) affecting patient survival, increasing the risk of dying before one year of follow-up by 2.7 times. DISCUSSION: Our study stands for the standalone hip prosthesis dislocation entailing a higher risk of death after hip fracture hemiarthroplasty in the older population.

Effect of hip hemiarthroplasty dislocation on mortality after hip fracture surgery.

INTRODUCTION: Hip arthroplasty is the treatment of choice for displaced femoral neck fractures among the older population. The hip prosthesis dislocation is one of the most pointed potential complications after hip arthroplasty, but there is a lack of updated information on the effect of dislocation on the survival of older hip fracture patients so treated by hip hemiarthroplasty. We aim to evaluate the standalone effect of hip prosthesis dislocation after hip fracture hemiarthroplasty on patients' survival outcomes. MATERIALS AND METHODS: We conducted a retrospective multicenter study, including 6631 femoral neck fracture patients over 65 surgically treated by hemiarthroplasty. We made follow-up cut-offs 30-days, 6 weeks, 90-days, and one year after hospital discharge determining hip dislocation rate and patients' survival. RESULTS: The women population represented 78.7%, and the mean age of the population was 85.2±6.7 years. Hip prosthesis dislocation incidence was 1.9% in the first 90-days after discharge, representing 91.54% of primary dislocations yearly noted. We reported statistically significant increased mortality rates of patients presenting at least one hip prosthesis dislocation event (from 16.0% to 24.6% at 90-day after discharge, and 29.5% to 44.7% at one year), and also significantly decreasing patient survival function at 90-day (p=0.016) and one-year follow-up (p<0.001). The recurrent dislocation events (26.15%) showed even higher mortality rates (up to 60.6%, p<0.001). The multivariate Cox regression model determined that prosthesis dislocation was the only significant variable (p=0.035) affecting patient survival, increasing the risk of dying before one year of follow-up by 2.7 times. DISCUSSION: Our study stands for the standalone hip prosthesis dislocation entailing a higher risk of death after hip fracture hemiarthroplasty in the older population.

Treatment of osteoporosis and hip fractures in a Spanish health area.

OBJECTIVE: The aim of this longitudinal retrospective ecological study was to evaluate the consumption of anti-osteoporotic medications and the evolution of pertrochanteric and femoral neck (FN), subtrochanteric and diaphyseal hip fractures between 2005 and 2010. MATERIALS AND METHODS: Data were obtained from our Hospital Admissions Service (absolute number of fractures) and the Technical Directorate of Pharmacy (defined daily dose and absolute number of containers consumed of bisphosphonates (BP), raloxifene and strontium ranelate). RESULTS: The overall incidence density of FN in 2005-2010 was 124.8 new cases per 100,000 persons per year. BP consumption increased between 2005 and 2010 to a peak of 70,452 containers consumed in 2010, while consumption of raloxifene declined. The number of subtrochanteric and diaphyseal fractures remained stable, but FN reached a peak in 2008 (N = 350) and fell thereafter (N = 284 in 2010). The percentage reduction in the number of FN in the period studied (2009: -14% and 2010: -11% compared to 2005) corresponds temporally with the increased consumption of BP (2009: +76% and 2010: +84% compared to 2005). CONCLUSIONS: We found an inverse temporal association between the annual consumption of BP and the annual number of FN during 2005-2010. This is probably related to the cumulative effect of BP, although, given the limitations of the study design, other studies are needed to confirm our data.

Dopamine enhances somatostatin receptor-mediated inhibition of adenylate cyclase in rat striatum and hippocampus.

Although there is evidence that suggests that dopamine (DA) has stimulatory effects on somatostatinergic transmission, it is unknown to date if DA increases the activity of the somatostatin (SS) receptor-effector system in the rat brain. In this study, we evaluated the effects of the administration of DA and the DA D1-like (D1, D5) receptor antagonist SCH 23390 and the D2-like (D2, D3, D4) receptor antagonist spiperone on the SS receptor-adenylate cyclase (AC) system in the Sprague-Dawley rat striatum and hippocampus. An intracerebroventricular injection of DA (0.5 microgram/rat) increased the number of SS receptors and decreased their apparent affinity in the striatum and hippocampus 15 hr after its administration. The simultaneous administration of the DA receptor antagonists SCH 23390 (0.25 mg/kg, ip) and spiperone (0.1 mg/kg, ip) before DA injection partially prevented the DA-induced increase in SS binding. The administration of SCH 23390 plus spiperone alone produced a significant decrease in the number of SS receptors in both brain areas studied at 15 hr after injection, an effect that disappeared at 24 hr. The increased number of SS receptors in the DA-treated rats was associated with an increased capacity of SS to inhibit basal and forskolin (FK)-stimulated (AC) activity in the striatum and hippocampus at 15 hr after injection. This effect had disappeared at 24 hr. By contrast, basal and FK-stimulated enzyme activities were unaltered after DA injection. No significant changes in the levels of the alpha i (alpha i1 + alpha i2) subunits were found in DA-treated rats as compared with control rats. In addition, the immunodetection of the alpha i1 or alpha i2 subunits showed no significant changes in their levels in DA-treated rats when compared with controls. DA injection also induced an increase in SS-like immunoreactive content in the rat striatum but not hippocampus at 15 hr after administration and returned to control values at 24 hr. These results provide direct evidence of a functional linkage between the dopaminergic and somatostatinergic systems at the molecular level.

Alpha-2 adrenoceptors modulate the somatostatinergic system and G protein levels in the rat hippocampus.

alpha 2-Adrenoceptor agonists and somatostatin (SS) exert opposite effects on the spike discharge of pyramidal and granule cells in the rat hippocampus. We studied whether clonidine, an alpha 2-adrenoceptor agonist, and yohimbine, an alpha 2-adrenoceptor antagonist, can modulate somatostatin-like immunoreactivity (SSLI) levels, binding of 125I-Tyr11-somatostatin (125I-Tyr11-SS) to its specific receptors, SS-inhibited adenylyl cyclase (AC) activity, and the guanine-nucleotide binding regulatory proteins Gi and G(o) in the rat hippocampus. Clonidine (1 mg/kg, intraperitoneally (IP) or yohimbine (5 mg/kg, IP) injected at both 10 and 16 hours before decapitation did not affect SSLI content in the hippocampus. Clonidine administration decreased the number of specific SS receptors and increased the apparent affinity in hippocampal membranes. This change in SS binding was not the result of a direct effect of clonidine on these receptors because no effect in binding was produced by high concentrations of clonidine (10(-5) M) when added in vitro. Pretreatment with yohimbine prevented the clonidine-induced in SS binding. Yohimbine alone produced a significant increase in the number of 125I-Tyr11-SS receptors and a decrease in its apparent affinity. Clonidine decreased the ADP-ribosylation of a 41- and a 39-kDa G-protein by pertussis toxin (PTX), whereas yohimbine had no effect on the PTX-catalyzed ADP-ribosylation. No significant differences were seen for the basal or for the forskolin (FK)-stimulated AC enzyme activities in the control, clonidine- and/or yohimbine-treated groups. Somatostatin caused a significantly lower inhibition in AC activity in hippocampal membranes of clonidine-treated rats, whereas yohimbine led to an opposite effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of phenylephrine and prazosin on the somatostatinergic system in the rat frontoparietal cortex.

Somatostatin (SS) and noradrenaline (NA) are distributed in the rat cerebral cortex, and seizure activity is one of the aspects of behavior affected by both neurotransmitters. Due to the possible interaction between both neurotransmitter systems, we studied whether phenylphrine, an alpha 1-adrenoceptor agonist, and prazosin, an alpha 1-adrenoceptor antagonist, can modulate SS-like immunoreactivity (SS-LI) levels, binding of [125I][Tyr11]SS to its specific receptors, the ability of SS to inhibit adenylate cyclase (AC) activity, and the guanine nucleotide binding regulatory protein G, and G., in the Sprague-Dawley rat frontoparietal cortex. An IP dose of 2 or 4 mg/kg of phenylephrine injected 7 h before decapitation decreased the number of SS receptors and increased the apparent affinity in frontoparietal cortex membranes. An IP dose of 20 or 25 mg/kg of prazosin administered 8 h before decapitation increased the number of SS receptors and decreased their apparent affinity. The administration of prazosin before the phenylephrine injection prevented the phenylephrine-induced changes in SS binding. The addition of phenylephrine and/or prazosin 10(-5) M to the incubation medium changed neither the number nor the affinity of the SS receptors in the frontoparietal cortex membranes. Phenylephrine or prazosin affected neither SS-LI content nor the basal or forskolin (FK)-stimulated AC activities in the frontoparietal cortex. In addition, SS caused an equal inhibition of AC activity in frontoparietal cortex membranes of phenylephrine-and prazosintreated rats compared with the respective control group. Finally, phenylephrine and prazosin did not vary the pertussis toxin (PTX)-catalyzed ADP ribosylation of Gi- and/or Go-proteins. These results suggest that the above-mentioned changes are related to the phenylephrine activation of alpha 1-adrenoceptors or to the blocking of these receptors by prazosin. In addition, these data provide further support for a functional interrelationship between the alpha 1-adrenergic and somatostatinergic systems in the rat frontoparietal cortex.

Somatostatin receptors coupled to the inhibition of adenylyl cyclase in the rat frontoparietal cortex are modulated by alpha 2 adrenoceptors.

The administration of an alpha 2-adrenoceptor agonist, clonidine, increased the number of somatostatin (SS) receptors and the affinity constant in frontoparietal cortex membranes. In addition, in the clonidine group, the capacity of SS to inhibit basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity in the frontoparietal cortex was significantly higher than in the control group. Pretreatment with the alpha 2-adrenoceptor antagonist yohimbine prevented the clonidine-induced changes in SS binding and SS-inhibited AC activity. Yohimbine alone had an opposite effect from clonidine. These experiments provide further evidence that the alpha-adrenergic system modulates the rat frontoparietal cortex somatostatinergic system.

Changes in alpha 1-adrenergic neurotransmission alter the number of somatostatin receptors in the rat hippocampus.

The administration of an i.p. dose of phenylephrine (2 mg/kg) increased the number of [125I]Tyr11-somatostatin ([125I]Tyr11-SS) receptors and decreased their apparent affinity in rat hippocampal membranes 7 h after its injection. Prazosin (20 mg/kg, i.p.) administered 1 h before phenylephrine reversed effects of the latter on SS binding. Prazosin alone decreased the number of SS receptors without changing the affinity. The addition of phenylephrine or prazosin (10(-5) M) to the incubation medium did not change the SS binding characteristics. The present results support the notion that the alpha 1-adrenergic system regulates the binding of SS to its specific receptors in rat hippocampus.

Beta-adrenergic regulation of the somatostatinergic system in rat hippocampus.

Interaction of beta-adrenergic and somatostatinergic systems in the hippocampus has not been investigated fully. We studied the influence of DL-isoproterenol (ISO), a beta-adrenergic agonist and DL-propranolol (PRO), a beta-adrenergic blocking agent, on the somatostatinergic system in the rat hippocampus. The short-(5h) and long-term (14 days) administration of ISO (5 mg/kg i.p.) or of PRO (10 mg/kg i.p.) did not affect somatostatin-like immunoreactivity (SSLI) content in the hippocampus of male Wistar rats. Both short- and long-term ISO administration decreased the number of specific [125I]Tyr11-somatostatin ([125I]Tyr11-SS) receptors in synaptosomes from hippocampus (29%, P < 0.05 and 34%, P < 0.05, after short- and long-term administration, respectively) without changing the affinity constant. This decrease in the number of [125I]Tyr11-SS receptors was not due to a direct effect of ISO on these receptors since no decrease in binding was produced by high concentrations of ISO (10(-5) M) when added in vitro. In addition, this decrease could be blocked by pretreatment with PRO. Short- and long-term administration of PRO alone increased the [125I]Tyr11-SS binding in hippocampus (42%, P < 0.05 and 33%, P < 0.05, after short- or long-term administration, respectively) without changing the affinity constant. Although there is no direct evidence that the regulation of SS receptors by the beta-adrenergic system has a physiological significance, this mechanism may provide a means by which the brain environment could modulate SS receptor number and, therefore, sensitivity to SS in a subset of SS-sensitive neurons.

Modulation by isoproterenol and propranolol of somatostatin receptors in synaptosomes from rat frontoparietal cortex.

DL-Propranolol (PRO), a beta-adrenergic blocking agent, and the neuropeptide somatostatin (SS) have central nervous system depressant and anticonvulsive properties. To investigate a possible relationship between these two components, we studied the influence of PRO and DL-isoproterenol (ISO), a beta-adrenergic agonist, on the somatostatinergic system in the rat frontoparietal cortex. The short- (5 h) and long-term (14 days) administration of ISO (5 mg/kg, intraperitoneally (i.p.)), or of PRO (10 mg/kg, i.p.) did not affect somatostatin-like immunoreactivity (SLI) content in the frontoparietal cortex of male Wistar rats. Both short- and long-term ISO administration decreased the number of specific [125I]Tyr11-SS receptors in synaptosomes from frontoparietal cortex (31%, P < 0.05, and 26%, P < 0.02, after short- and long-term administration, respectively) without changing the affinity constant. This decrease in the number of [125I]Tyr11-SS receptors was not due to a direct effect of ISO on these receptors since no decrease in binding was produced by high concentrations of ISO (10(-5) M) when added in vitro. This decrease could be blocked by pretreatment with PRO. Short- and long-term administration of PRO alone produced an increase in the [125I]Tyr11-SS binding in frontoparietal cortex (26%, P < 0.02, and 40%, P < 0.001, after short- or long-term administration, respectively) without changing the affinity constant.

Effect of serotonin axon injury on the somatostatinergic system in rat frontoparietal cortex.

In order to investigate the possibility that, in the rat, some cerebral cortex somatostatin (SS) receptors may be localized presynaptically on the terminals of serotonergic neurons, serotonin [5-hydroxytryptamine, (5-HT)] neurons in the central nervous system were damaged with a local intracerebral injection of the serotonergic neurotoxin, 5,7-dihydroxytryptamine(5,7-DHT). The injection of 5,7-DHT (11 micrograms free base dissolved in 10 microliters of isotonic saline containing 0.01% ascorbic acid) in rats produced an reduction by about 74% in frontoparietal cortical 5-HT content at 1 and 3 weeks after injection. These changes were associated with a significant decrease by about 30% in the total number of specific SS receptors in the frontoparietal cortex at both times studied without influencing the apparent affinity of the receptors. Together, these results suggest that a portion of the frontoparietal cortex SS receptors may be localized presynaptically on the serotonergic nerve terminals. The 5,7-DHT did not affect SS-like immunoreactivity (SSLI) levels suggesting that SS and 5-HT are not colocalized within the same neuronal elements in the rat frontoparietal cortex.

Desmethylimipramine pretreatment prevents 6-hydroxydopamine induced somatostatin receptor reduction in the rat hippocampus.

Several studies have shown anatomical and functional interconnections between catecholaminergic and somatostatinergic systems. To assess whether somatostatin (SS) may act presynaptically on catecholamine neurons, SS receptors were measured using radioligand test-tube binding assays on synaptosomes from hippocampus and frontoparietal cortex--areas that are innervated by catecholaminergic neurons with different densities and that have a high number of SS receptors--from control and 6-hydroxydopamine (6-OHDA)-treated rats. Intracerebroventricular (i.c.v.) injection of the catecholamine neurotoxin 6-OHDA (0.78 mg free base/kg of body weight in saline with 0.1% ascorbic acid) lowered hippocampal and frontoparietal cortical noradrenaline (NA) and dopamine (DA) levels at 1 week following the injection. Pretreatment of rats with desmethylimipramine (DMI) (40 mg/kg, intraperitoneal) prevented the drop in NA levels, but was not effective in attenuating DA depletion in the two brain areas studied. Treatment with 6-OHDA lowered the number of 125I-Tyr11-SS receptors in the hippocampus (130 +/- 19 vs. 266 +/- 16 fmol/mg protein, P < 0.001), whereas in the frontoparietal cortex a non significant 20% reduction in receptor number was found. The dissociation constants of 125I-Tyr11-SS binding to synaptosomes from frontoparietal cortex (0.65 +/- 0.06 vs. 0.60 +/- 0.04, P not significant) and hippocampus (0.44 +/- 0.04 vs. 0.63 +/- 0.14, P not significant) were similar in control and treated groups. Pretreatment with DMI reversed up to 80% of the effect of 6-OHDA on hippocampus SS receptors. DMI alone had no observable effect on the number and affinity of SS receptors. The 6-OHDA and the DMI treatment did not affect SLI levels in the brain areas studied. These results suggest that a portion of the hippocampal SS receptors may be localized presynaptically on the noradrenergic and dopaminergic nerve terminals.

Reduction of somatostatin receptors in rat hippocampus by treatment with 5,7-dihydroxytryptamine.

Several lines of evidence suggest that somatostatin (SS) may interact with serotonergic neurons in the central nervous system. To assess whether SS acts presynaptically on serotonin (5-hydroxytryptamine, (5-HT)) neurons, SS receptors were measured in membranes from the hippocampus, a brain region that receives dense serotonergic innervation and has a high number of SS receptors in control and 5,7-dihydroxytryptamine (5,7-DHT)-treated rats, at 1 and 3 weeks after injection. Intracerebroventricular (i.c.v.) injection of the 5-HT-specific neurotoxin 5,7-DHT (11 micrograms (free base) dissolved in 10 microliters of isotonic saline containing 0.01% ascorbic acid) produced a 70% reduction in hippocampal 5-HT content at 3 weeks after injection but not at 1 week. This change was associated with a significant decrease in SS receptor density in rat hippocampus only at 3 weeks following the injection, without influencing the apparent affinity of the receptors at any time. Administration of 5,7-DHT did not affect somatostatin-like immunoreactivity (SSLI) levels at both times studied. These results suggest that some of the hippocampal SS receptors may be localized presynaptically on the serotonergic nerve terminals.