Biomedical subjects

D C Perry

Publications and source records attributed to D C Perry.

At least 19 recordsLinked to original sources

PubMed2001

Evidence of a functional alpha7-neuronal nicotinic receptor subtype located on motoneurons of the dorsal motor nucleus of the vagus.

In vitro autoradiography using 125I-alpha-bungarotoxin (alpha-BGTx) and anti-alpha7 immunohistochemistry were performed on the dorsal motor nucleus of the vagus (DMV) of sham and chronically vagotomized rats to determine whether the alpha7-nicotinic acetylcholine receptor (nAChR) is located postsynaptically on DMV neurons whose axons contribute to the vagus nerve. Intense bilateral 125I-alpha-BGTx binding and anti-alpha7 immunostaining were observed in coronal brain sections containing the DMV of sham-vagotomized animals. Unilateral cervical vagotomy resulted in ipsilateral losses of 125I-alpha-BGTx binding and anti-alpha7 immunostaining from the DMV. Simultaneous staining of rat brainstem sections with anti-alpha7 and anti-choline acetyltransferase (ChAT) antibodies (to identify cholinergic DMV neurons that project into the vagus nerve) revealed that every DMV neuron that was stained for ChAT showed alpha7-staining as well. In vagotomized animals, no ChAT-positive neurons expressing alpha7-nAChRs remained in the ipsilateral DMV. We conclude that the alpha7-nAChR subtype is located postsynaptically on DMV neurons. To test whether the alpha7-nAChR is similar to the alpha7-homomeric nAChR, experiments were performed in anesthetized rats, and compounds were microinjected into the DMV while monitoring intragastric pressure (IGP). alpha-BGTx and strychnine antagonized nicotine-induced increases in IGP; no antagonism was observed with methyllycaconitine, a compound known to block the homomeric alpha7-nAChR subtype. Recovery from alpha-BGTx-induced antagonism of the nicotine response was observed. We conclude that there is a nAChR containing the alpha7-subunit in the DMV that is different from the homomeric alpha7-nAChR subtype.

Aconitine↗

PubMed2000

Prenatal nicotine exposure: effects on locomotor activity and central [125I]alpha-BT binding in rats.

Maternal smoking during pregnancy or in utero exposure of the fetus to nicotine may result in learning difficulties and hyperactivity in the child. To elucidate possible involvement of the alpha(7) nicotinic receptor subtype in these behavioral impairments, pregnant dams were treated with nicotine (9 mg/kg/day) via osmotic minipumps throughout gestation. Male offspring were weaned at postnatal day 18, and were tested for locomotor activity at postnatal days 20-24. Pups were sacrificed on postnatal day 36-38 and 18 discrete brain areas were analyzed for [125I]alpha-bungarotoxin (alpha-BT) binding by quantitative autoradiography. Prenatal nicotine caused an elevation in locomotor activity (vertical movements) in offspring. [125I]alpha-BT binding was significantly reduced in the hippocampal CA1 region (29%), dentate gyrus (22%), and medial geniculate nucleus (29%). These findings suggest that some of the behavioral abnormalities induced by prenatal nicotine exposure may be due to a reduction of alpha(7) nicotinic receptors in discrete brain regions.

Animals↗

PubMed2000

Prenatal nicotine exposure is associated with an increase in [125I]epibatidine binding in discrete cortical regions in rats.

Previously, it was reported that hyperactive male offspring of dams exposed to nicotine (6 mg/kg/day) during gestation had an increase in cortical alpha4-beta2 nicotinic receptor subtype density as determined by [3H]cytisine binding in tissue homogenate [Tizabi Y, Popke EJ, Rahman MA, Nespor SM, Grunberg NE. Hyperactivity induced by prenatal nicotine exposure is associated with an increase in cortical nicotinic receptors. Pharmacol, Biochem Behav 1997;58:141-6]. [125I]Epibatidine labels alpha4beta2 nicotinic receptors with higher affinity than [3H]cytisine. In the present study, using quantitative autoradiography, we evaluated the effects of in-utero exposure to nicotine (9 mg/kg/day) on [125I]epibatidine binding in 46 discrete brain regions of 36-day-old male offspring of Sprague-Dawley rats. This dosage of nicotine administered during pregnancy to same rats was shown to result in increased vertical activity in the male offspring [Tizabi Y, Russell LT, Nespor SM, Perry DC, Grunberg NE. Prenatal nicotine exposure: effects on locomotor activity and central [125I]alpha-BT binding in rats. Pharmacol, Biochem Behav (in press).]. Prenatal nicotine exposure resulted in increases in receptor densities of the somatosensory cortex (90%) and the visual cortex (107%) only. Moreover, these increases were restricted to cortical layer 1. Collectively, these results indicate that prenatal nicotine exposure affects specific nicotinic receptors in selective cortical regions of male offspring. These neurochemical effects may be responsible for some of the behavioral abnormalities seen in such offspring.

Animals↗

PubMed1999

Increased nicotinic receptors in brains from smokers: membrane binding and autoradiography studies.

Chronic administration of nicotine increases the density of neuronal cholinergic nicotinic receptors in cells and in rodent brain, and similar increases have been reported in brains from human smokers. To further examine this phenomenon, we measured nicotinic receptor binding sites in brain regions from matched populations of smokers and nonsmokers. We first measured binding of [3H](+/-)epibatidine ([3H]EB) and [3H]cytisine in homogenate preparations from samples of prefrontal and temporal cerebral cortex. Binding of each radioligand was significantly higher (250-300%) in both cortical regions from brains of smokers. Frozen sections from each of the cerebral cortical regions and the hippocampus were used for autoradiographic analysis of [3H]EB binding. In cerebral cortex, binding was most dense in layer VI in the prefrontal cortex and layers IV and VI in the temporal cortex. Densitometric analysis of [3H]EB binding sites revealed marked increases of 300 to 400% of control in all cortical regions examined from smokers' brains. Binding in the hippocampal formation was heterogeneously distributed, with dense areas of binding sites seen in the parasubiculum, subiculum, and molecular layer of the dentate gyrus, and the lacunosum-moleculare layer of the CA1/2. Binding of [3H]EB was significantly higher in all six regions of the hippocampus examined from brains of smokers compared with nonsmokers. These increases ranged from 160% of control in parasubiculum to 290% in the molecular layer of the dentate gyrus. The increase in nicotinic receptors in the cerebral cortex and hippocampus of smokers may modify the central nervous system effects of nicotine and contribute to an altered response of smokers to nicotine.

Adult↗

PubMed1998

Bcl-2 protects against apoptosis in neuronal cell line caused by thapsigargin-induced depletion of intracellular calcium stores.

The toxicity of thapsigargin, a selective inhibitor of endoplasmic reticular Ca2+-ATPase, was investigated in GT1-7 cells, a murine hypothalamic cell line. Treatment of these cells with 50 or 100 nM thapsigargin greatly reduced cell viability at 24 and 48 h. These doses of thapsigargin induced a rapid rise in free cytosolic Ca2+ ([Ca2+]i), followed by a sustained increase. Addition of EGTA to chelate extracellular Ca2+ diminished somewhat the size of the initial increase of [Ca2+]i caused by thapsigargin, and abolished the sustained increase. The sustained increase could also be abolished by addition of La3+ and by SKF 96365, a drug selective for receptor-mediated calcium entry, but not by verapamil or flunarizine. Pretreatment with 50 microM BAPTA/AM, a cytosolic Ca2+ chelator, inhibited the peak [Ca2+]i caused by thapsigargin but did not inhibit the sustained elevation of [Ca2+]i. Neither EGTA nor BAPTA/AM inhibited the cell death induced by thapsigargin. The cell death was characterized by DNA fragmentation ("laddering"), nuclear condensation and fragmentation, and was inhibited by protein synthesis inhibitor cycloheximide, all characteristic of apoptotic cell death. Overexpression of the protooncogene bcl-2 in GT1-7 cells inhibited significantly DNA fragmentation, nuclear condensation and fragmentation, and cell death induced by thapsigargin. However, Bcl-2 did not alter either basal [Ca2+]i or the elevation of [Ca2+]i induced by thapsigargin. Our results suggest that abnormal Ca2+ release from endoplasmic reticulum caused by thapsigargin induces GT1-7 death by apoptosis and that this effect does not depend on Ca2+ influx from the extracellular space. Bcl-2 inhibited apoptosis induced by thapsigargin, but the mechanism is unlikely to be inhibition of endoplasmic reticular Ca2+ release in GT1-7 neuronal cells.

Animals↗

PubMed1997

Acetabular fractures.

There are many questions that remain to be answered regarding the evaluation, classification, and treatment of acetabulum fractures. Without a uniform classification and method of evaluation, a review of the literature can be misleading. Acetabular fractures represent an injury to the articular surface of a major weight-bearing joint and should be treated in accordance with the same criteria used for other intra-articular fractures.

Acetabulum↗

PubMed1997

[125I]IPH, an epibatidine analog, binds with high affinity to neuronal nicotinic cholinergic receptors.

An analog of epibatidine (EB) was synthesized with an iodine atom in the 2 position of the pyridyl ring. This analog, (+/-)-exo-2-(2-iodo-5-pyridyl)-7-azabicyclo[2.2.1]heptane (IPH), as well as its two stereoisomers, displayed high affinity for neuronal nicotinic receptors; therefore, radioiodinated IPH, [125I]IPH, was synthesized with specific radioactivities consistently > 1000 Ci/mmol, and its properties as a radioligand for neuronal nicotinic receptors were evaluated. The characteristics of [125I]IPH binding in tissue homogenates appeared to be virtually identical to those reported for [3H]epibatidine binding; but the high specific radioactivity of [125I]IPH greatly facilitated measurements of nicotinic receptors in tissues with relatively low receptor densities and/or where tissues are in limited supply. Autoradiography with [125I]IPH provided clear localization of nicotinic receptors in brain and adrenal gland after film exposure times of < or = 2 days. We conclude that [125I]IPH will be a very useful radioligand for the study of neuronal nicotinic receptors in brain and in peripheral ganglia.

Animals↗

PubMed1996

Non-NMDA glutamate receptor binding in canine brain after global cerebral ischemia and reperfusion.

We employed a canine model to test the effects of global cerebral ischemia and reperfusion on binding to alpha-amino-3-hydroxy-5-methyl- 4-isoxazole proprionate (AMPA), kainate (KA), and metabotropic glutamate receptors. Ischemia was induced by 10 min of cardiac arrest, followed by restoration of spontaneous circulation for periods of 0, 0.5, 2, 4, and 24 h. Frozen sections were prepared from parietal and temporal cortex, hippocampus, and striatum, and in vitro autoradiography was performed with one of three radioligands: [3H]AMPA, [3H]KA, or [3H] glutamate (using conditions allowing specific labeling of the metabotropic binding site). In striatum, metabotropic binding was unchanged, whereas AMPA and KA binding decreased by 20-30% at 30 min postischemia, remaining depressed through 24 h. In cortex, AMPA and metabotropic binding were decreased at several time-points after ischemia and recirculation, particularly in parietal cortex, whereas KA binding was unaffected in this tissue. Binding to hippocampal regions was largely unchanged, except for a decrease in KA binding at 2 and 4 h postischemia. These findings contrast with results from parallel studies showing increased striatal binding to NMDA receptors following ischemia. Decreased binding to non-NMDA glutamate receptors in striatum and parietal cortex may serve to protect against damage mediated through these receptors.

Animals↗

PubMed1996

Dantrolene is cytoprotective in two models of neuronal cell death.

The neuroprotective effects of dantrolene, an inhibitor of calcium release from intracellular stores, were investigated in a model of cell death induced by calcium release from endoplasmic reticulum in vitro. Thapsigargin (50 nM), a selective inhibitor of endoplasmic reticular Ca(2+)-ATPase, significantly increased the cytosolic Ca2+ concentration to 230% over basal levels, induced DNA fragmentation, and reduced cell viability from 94% in control cells to 41% after a 24-h treatment in GT1-7 hypothalamic neurosecretory cells. Pretreatment with dantrolene for 30 min significantly inhibited elevation of cytosolic Ca2+ levels, DNA fragmentation, and GT1-7 cell death induced by thapsigargin in a dose-dependent manner. To determine if dantrolene would also be protective in an in vivo model of neurodegeneration, it was administered intravenously immediately following a 5-min global cerebral ischemia in gerbils, and the number of intact hippocampal CA1 pyramidal neurons was counted 7 days later. The effects of dantrolene on brain and rectal temperature were monitored in a separate experiment. Dantrolene significantly increased the number of intact CA1 pyramidal neurons from 40% (untreated ischemic animals) to 67 (10 mg/kg), 78 (25 mg/kg), or 83% (50 mg/kg) of values in sham controls (all p < 0.001). No significant changes in brain or rectal temperature were detected for 4 h following 50 mg/kg dantrolene. These results suggest that abnormal Ca2+ release from intracellular stores can induce neuronal death and that such a mechanism may contribute to delayed hippocampal neuronal death after cerebral ischemia. Dantrolene may be a potentially useful drug for neuroprotection after cerebral ischemia.

Animals↗

PubMed1996

Prediction of situational awareness in F-15 pilots.

Situational awareness (SA) is a skill often deemed essential to pilot performance in both combat and noncombat flying. A study was conducted to determine if SA in U.S. Air Force F-15 pilots could be predicted. The participants were 171 active duty F-15 A/C pilots who completed a test battery representative of various psychological constructs proposed or demonstrated to be valid for the prediction of performance in a wide variety of military and civilian jobs. These predictors encompassed measures of cognitive ability, psychomotor ability, and personality. Supervisor and peer ratings of SA were collected. Supervisors and peers showed substantial agreement on the SA ratings of the pilots. The first unrotated principle component extracted from the supervisor and peer ratings accounted for 92.5% of the variability of ratings. The unrotated first principal component served as the SA criterion. Flying experience measured in number of F-15 hours was the best predictor of SA. After controlling for the effects of F-15 flying hours, the measures of general cognitive ability based on working memory, spatial reasoning, and divided attention were found to be predictive of SA. Psychomotor and personality measures were not predictive. With additional F-15 flying hours it is expected that pilots would improve their ratings of SA.

Adult↗

PubMed1995

[3H]epibatidine labels nicotinic receptors in rat brain: an autoradiographic study.

Epibatidine, a frog skin alkaloid, is a nicotinic receptor agonist with potent analgesic activity. We used in vitro receptor autoradiographic techniques to map binding sites for [3H]epibatidine in rat brain, and those for another nicotinic agonist, [3H]cytisine. Both [3H]epibatidine and [3H]cytisine are excellent radioligands for autoradiography. [3H]Epibatidine in particular binds with very high affinity and extremely low nonspecific binding. In the present study, the distribution of binding was almost identical for both radioligands and closely resembled that of previously published autoradiographic studies with two other nicotinic ligands, [3H]acetylcholine and [3H]nicotine. Brain regions demonstrating the highest levels of [3H]epibatidine binding included the interpeduncular nucleus, medial habenular nucleus, fasciculus retroflexus, superficial gray layer of the superior colliculus and numerous thalamic nuclei, including the anteroventral, dorsal lateral geniculate and gelatinosus nuclei. Quantitative analysis revealed that [3H]epibatidine binding was greater than [3H]cytisine binding in several regions. In particular, [3H]epibatidine clearly labeled the optic nerve, optic chiasm and optic tract, whereas [3H]cytisine binding to these structures did not exceed background levels. Other regions in which [3H]epibatidine binding was greater than that of [3H]cytisine included the medial habenula, fasciculus retroflexus, olivary pretectal nucleus and superficial gray layer of the superior colliculus. The differences in labeling between these two nicotinic ligands may arise from receptor heterogeneity in brain nicotinic receptors and the ability of [3H]epibatidine to label more than one subtype of nicotine receptor.

Animals↗

PubMed1994

Autoradiographic analysis of L- and N-type voltage-dependent calcium channel binding in canine brain after global cerebral ischemia/reperfusion.

Binding of antagonists to L- and N-type voltage-dependent calcium channels (VDCC) was measured in canine brain following global ischemia and reperfusion. Ischemia was induced by 10 min cardiac arrest, followed by restoration of spontaneous circulation for periods of up to 24 h. Binding of [3H]PN200-110 and [125I]omega-conotoxin GVIA to frozen sections from hippocampus, striatum, parietal cortex and temporal cortex was analyzed using quantitative receptor autoradiography. The binding patterns of the two radioligands were similar in cortex and striatum, but differed in hippocampus. In the latter tissue, [125I]omega-conotoxin GVIA binding was dense over synaptic regions, especially the presynaptic polymorph layer of the dentate gyrus, but was virtually absent over cell body layers. In contrast, [3H]PN200-110 binding was more homogenously distributed, with highest binding in the molecular layer of the dentate gyrus. The binding of [125I]omega-conotoxin GVIA was not different from sham controls at any time point following cardiac arrest. [3H]PN200-110 binding was decreased in each region immediately following ischemia, recovering within 30 min of recirculation. These findings are in contrast to earlier findings of rapid increases in L-type VDCC binding to membrane fractions obtained from cortex and striatum in this model, and suggest that the previously detected increases may be due to a redistribution of channels from subcellular compartments to the plasma membrane during ischemia.

Animals↗

PubMed1993

Forebrain ischemia in the gerbil increases lambda opiate binding in hippocampal mossy fibers.

Transient forebrain ischemia was produced in gerbils by short-term occlusion of the common carotid arteries under halothane anesthesia. Histological analysis of brains 7 days post-ischemia demonstrated characteristic destruction of CA1 pyramidal cells. lambda Opiate binding (measured with [3H]naloxone in the presence of 300 nM diprenorphine) at 7 days post-ischemia was significantly increased in the stratum lucidum of the hippocampus (the mossy fiber layer), but not in any other region measured, including other hippocampal regions, cortex, amygdala, caudate putamen, thalamus, and hypothalamus. The increase in mossy fiber lambda binding was slow to develop (no increase detected up to 48 h post-ischemia), and long-lasting (binding remained elevated at 32 days post-ischemia). While MK-801 significantly inhibited CA1 pyramidal cell destruction when administered 20 min prior to ischemia, the increase in mossy fiber lambda binding was still evident. None of seven different opioid agonists and antagonists examined had an effect on either the pyramidal cell damage or increased mossy fiber lambda binding seen 7 days after ischemia.

Afferent Pathways↗

PubMed1992

Chronic reserpine administration selectively up-regulates beta 1- and alpha 1b-adrenergic receptors in rat brain: an autoradiographic study.

Rats were treated for 15 days with reserpine or vehicle. One day after the last treatment, animals were killed and frozen brain sections were prepared for in vitro autoradiography. Binding to beta-adrenergic receptors was measured with [125I]iodocyanopindolol, and binding selective for beta 1 and beta 2 subtypes was assessed by including non-radioactive drugs that selectively mask beta receptor subtypes. Total alpha 1-adrenergic receptor binding was measured with [3H]prazosin, while alpha 1a binding was measured with [3H]WB4101 (in the presence of unlabeled serotonin). Quantitative densitometric analysis revealed that chronic reserpine treatment caused an increase in beta binding throughout the brain, including the cortex, thalamus, amygdala, hippocampus, caudate-putamen and hypothalamus. This effect of reserpine was entirely confined to the beta 1 subtype in all regions examined. [3H]Prazosin binding (alpha 1a plus alpha 1b) was also increased after chronic reserpine in several regions of the cortex and thalamus, as well as the ventral hippocampus and caudal amygdala. No effect of chronic reserpine was seen on [3H]WB4101 binding, indicating that the effect of reserpine on alpha 1 receptors is limited to the alpha 1b subtype. The increase in alpha 1b binding after reserpine administration in rats was generally smaller and less widespread than that seen with beta 1 binding. Thus the effect of reserpine upon noradrenergic neurotransmission demonstrates a high degree of receptor specificity and regional selectivity.

Animals↗

PubMed1991

Electroconvulsive shock increases alpha 1b- but not alpha 1a-adrenoceptor binding sites in rat cerebral cortex.

Repeated administration of electroconvulsive shock (ECS) increases [3H]prazosin binding to alpha 1-adrenoceptors in rat cerebral cortex. In contrast, [3H]WB4101 binding in cortex has been reported to be unchanged after ECS. [3H]Prazosin labels two alpha 1-adrenoceptor subtypes, termed alpha 1a and alpha 1b, whereas [3H]WB4101 labels the alpha 1a subtype preferentially. The purpose of this study was to determine whether ECS increases one or both alpha 1-adrenoceptor subtypes in rat cerebral cortex. We found that treatment of rats with ECS once daily for 10-12 days increased [3H]prazosin binding in cortex by about 25% but did not significantly alter [3H]WB4101 binding to alpha 1-adrenoceptors. Measurement of alpha 1a and alpha 1b receptors by competition analysis of the selective alpha 1a antagonist 5-methylurapidil against [3H]prazosin and measurement of [3H]prazosin binding in homogenates preincubated with chlorethylclonidine, which alkylates alpha 1b binding sites, also indicated that the ECS-induced increase in alpha 1-adrenoceptors is confined to the alpha 1b subtype. In contrast to its effect on [3H]prazosin binding, ECS did not increase phosphoinositide hydrolysis as measured by [3H]inositol 1-phosphate accumulation in slices of rat cerebral cortex stimulated by either norepinephrine or phenylephrine. The failure of ECS to increase [3H]inositol 1-phosphate accumulation stimulated by phenylephrine, which is a partial agonist for this response, suggests that spare receptors do not account for the apparent absence of effect of ECS on alpha 1-adrenoceptor-mediated phosphoinositide hydrolysis.

Adrenergic beta-Antagonists↗

PubMed1990

Autoradiography of [3H]quipazine in rodent brain.

The distribution of binding sites for [3H]quipazine was examined in sections from rat brain. This radioligand has been demonstrated to label 5-HT3 receptors in membrane homogenate studies. Specificity of [3H]quipazine for these receptors was obtained by using 10(-7) M ICS 205-930, a highly selective 5-HT3 antagonist, to define non-specific binding. Several areas of dense 5-HT3-specific binding were detected in the medulla, most notably the nucleus of the solitary tract and the caudal portion of the spinal trigeminal tract. Low to moderate levels of 5-HT3 binding were seen in several forebrain regions, including the pyriform cortex, posterior nuclei of the amygdala, ventral tegmental area, anterior olfactory nucleus and superior colliculus. [3H]Quipazine autoradiography was also performed on brain sections from mouse, gerbil, hamster and guinea pig. Specific binding was quite low throughout most of the brains from these species; however, in all but the guinea pig, dense streaks of binding were detected in nucleus of the solitary tract (and in the mouse, the nucleus of the spinal tract of the trigeminal nerve). The distribution of 5-HT3 receptors in the brain may help explain some of the proposed CNS activities of 5-HT3-selective drugs. The anti-emetic and antinociceptive activities of 5-HT3 antagonists may be mediated by receptors in the sensory areas in the brainstem.

Animals↗

PubMed1990

Electroconvulsive shock differentially increases binding to alpha-1 adrenergic receptor subtypes in discrete regions of rat brain.

Quantitative in vitro autoradiographic methods were used to examine for the effect of repeated administration of electroconvulsive shock (ECS) on binding to subtypes of the alpha-1 receptor in rat brain. Rats were treated once daily for 10 d with ECS or sham ECS, then killed, and brains were removed and sectioned for autoradiographic analysis. Total alpha-1 binding (including both alpha-1a and alpha-1b subtypes) was assessed with [3H]prazosin; alpha-1b binding was assessed with [3H]prazosin in the presence of 10 nM WB4 101 to mask alpha-1a binding; and alpha-1a binding was assessed with [3H]WB4 101. ECS caused a significant increase in [3H]prazosin binding in most cortical regions: this increase was confined to a band corresponding to cortical laminae I-III. Subtype analysis indicated that the increase in cortical binding was due to an increase in binding to the alpha-1b subtype. Dense alpha-1 binding was detected in most thalamic nuclei: however, only 1 small area, the parafascicular nucleus, showed a significant increase in alpha-1 binding following repeated ECS. The only other region where ECS was shown to significantly affect alpha-1 binding was the amygdala. Binding to all regions of the amygdala except the central nuclei was increased by ECS: in the lateral amygdala, this was due primarily to an increase in alpha-1b binding, while in the remaining regions the increase was primarily an alpha-1a phenomenon. Thus the effect of repeated ECS on alpha-1 binding in rat brain was found to be confined to several specific regions of the cortex, thalamus, and amygdala. Furthermore, in each of these regions, the ECS effect was limited to 1 or the other of the 2 subtypes of the alpha-1 receptor.

Adrenergic alpha-Antagonists↗

PubMed1989

Opiate receptor subtype binding in gerbil hippocampus is altered by forebrain ischemia.

A role for endogenous opioids in trauma-induced brain injury has been supported by pharmacological studies. The present series of experiments were initiated to extend these observations by measuring opiate receptor subtype binding in gerbil hippocampus following 7 days recovery from a 10 min ischemic insult. Quantitative in vitro autoradiography was utilized to measure mu [( 3H]DAGO), kappa [( 3H]bremazocine + 10 microM morphiceptin + 100 nM DSLET), delta [( 3H]DSLET + 10 microM morphiceptin) and lambda [( 3H]naloxone + 300 nM diprenorphine) binding. While ischemic tissue samples at the level of the dorsal hippocampus showed complete loss of CA1 pyramidal cells, we observed no significant alterations in mu or delta binding suggesting a non-pyramidal cell localization of these receptors. Kappa binding decreased significantly to 88% of control in the CA1 and CA3 regions while lambda binding in the stratum lucidum (CA3) increased to 165% of control. Our results show that opiate receptor subtypes are differentially affected by an ischemic insult.

Animals↗