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Biomedical subjects

N L Ostrowski

Publications and source records attributed to N L Ostrowski.

29 records · Page 2Linked to original sources
PubMed1988

Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats.

Galanin coexists with acetylcholine in medial septal neurons projecting to the ventral hippocampus, a projection thought to modulate memory functions. Neurochemical lesions of the nucleus basalis-medial septal area in rats impaired choice accuracy on a delayed alternation t-maze task. Acetylcholine (7.5 or 10 micrograms intraventricularly or 1 micrograms micro-injected into the ventral hippocampus) significantly improved performance in the lesioned rats. Atropine (5 mg/kg intraperitoneally or 10 micrograms intraventricularly), but not mecamylamine (3 mg/kg intraperitoneally or 20 micrograms intraventricularly), blocked this action of acetylcholine, suggesting involvement of a muscarinic receptor. Galanin (100-500 ng intraventricularly or 200 ng into the ventral hippocampus) attenuated the ability of acetylcholine to reverse the deficit in working memory in the lesioned rats. The antagonistic interaction between galanin and acetylcholine suggests that endogenous galanin may inhibit cholinergic function in memory processes, particularly in pathologies such as Alzheimer disease that involve degeneration of basal forebrain neurons.

Acetylcholine↗
PubMed1987

Autoradiographic visualization of sex differences in the pattern and density of opiate receptors in hamster hypothalamus.

Slide-mounted brain sections were used to visualize the distribution of opiate receptors in the hypothalamus of male and female hamsters using the vitro film autoradiography. Sex differences were found in the binding density and patterns of [3H]naloxone-labeled receptors. The distribution and density of [3H][D-Ala2,D-Leu5]enkephalin-labeled delta-receptors in adjacent brain sections were similar in males and females. Male hamsters showed a U-shaped pattern of [3H]naloxone binding in the sexually dimorphic nuclear complex with 28% and 34% greater labeling of the sexually dimorphic nucleus (SDN) and bed nucleus/stria terminalis (BNST), respectively, than periovulatory estrous females. Estrous and diestrous females showed a V-shaped pattern of [3H]naloxone binding in the same region, but binding density was higher at diestrus. Greater specific [3H]naloxone binding in diestrous females was also evident following extensive prewashing of slide-mounted tissue sections indicating that residual endogenous opioids were not occupying receptors, and thus, reducing the labeling of receptors in tissue from estrous females. An estrous-linked change in the affinity of hypothalamic opiate receptors was suggested by findings that [3H]naloxone binding density was greater in tissue from diestrous females when incubations were conducted in the presence of a 1-nM, but not a 10-nM, concentration of the labeled antagonist. Finally, a dense are of [3H]naloxone binding was discovered in the dorso-suprachiasmatic region of the hypothalamus. These data provide evidence for a sexual dimorphism in the distribution and density of opiate receptors in hamsters. The data suggest that mu- or kappa-receptors are more likely than delta-receptors to be involved in mediating hypothalamic effects of endogenous and exogenous opioids on reproductive functions in this species.

Animals↗
PubMed1987

The pattern of [3H]cyclofoxy retention in rat brain after in vivo injection corresponds to the in vitro opiate receptor distribution.

Cyclofoxy, a fluorinated analog of naltrexone, has been designed specifically to permit in vivo labeling of opiate receptors in experimental animals and ultimately, humans. Recently, using positron emission tomography (PET), 3-[18F]acetylcyclofoxy was shown to accumulate in opiate receptor-rich brain regions of a live baboon and to be stereospecifically displaced by injections of (-)-naloxone but not (+)-naloxone. Autoradiographic evidence is presented here that the unacetylated compound, [3H]cyclofoxy, labels a population of opiate receptors in brain after in vivo injections that is virtually identical to that labeled by [3H]naloxone. The in vivo binding patterns of [3H]cyclofoxy in brain were similar to those obtained following incubation of slide-mounted brain sections in vitro. Intravenous injections of [3H]cyclofoxy to rats yielded high (greater than 4:1) striatal and thalamic to cerebellar binding ratios in brain homogenates, supernatants and in 24 micron-thick brain sections 60 min after 30 mu Ci per animal (spec. act. = 16.4 Ci/mmol). Autoradiographs revealed the typical opiate antagonist binding profile with marked retention of [3H]cyclofoxy in the striatal patches, subcallosal streak, medial habenula and central thalamus with little retention of label in cerebellum. [3H]Cyclofoxy binding was reversible since the radiolabeled drug disappeared from brain tissue within 2 h after injections to rats, or could be removed from brain slices in vitro by washing slide-mounted tissue sections for 45 min. In addition, after in vitro washing the same brain sections again bound [3H]cyclofoxy or [3H]naloxone in the same pattern. When pre-washed brain sections were incubated with [3H]cyclofoxy in the presence of unlabeled naloxone, [3H]cyclofoxy binding was reduced to background levels. These data show that [3H]cyclofoxy labels-sensitive opiate receptors in vivo and in vitro. The present results combined with evidence that cyclofoxy demonstrates a low level of toxicity in animals suggest that cyclofoxy is an excellent tool with which to study the physiological role of opiate receptors in living animals using in vivo autoradiography, and in humans using PET.

Animals↗
PubMed1987

Aldosterone-reversible decrease in the density of renal peripheral benzodiazepine receptors in the rat after adrenalectomy.

A statistically significant decrease in the density of peripheral benzodiazepine receptors was observed in renal membranes of rats beginning 2 weeks after adrenalectomy when compared with sham-operated controls. This decrease in peripheral benzodiazepine receptor density was manifest as a decrease in the maximum binding of two ligands, [3H]Ro 5-4864 and [3H]PK 11195, without accompanying changes in their Kd for this site. Similar changes were not seen in another aldosterone-sensitive organ, the submandibular salivary gland. The decrease in peripheral benzodiazepine receptor density observed in adrenalectomized rat renal membranes was restored to control levels after 1 week of aldosterone administration using a dose (12.5 micrograms/kg/day) that had no effect on peripheral benzodiazepine receptor density in sham-operated animals. In contrast, dexamethasone administration (50 micrograms/kg/day, 1 week) had no effect on renal peripheral benzodiazepine receptor density when administered to either adrenalectomized or sham-operated rats. Further, adrenal demedullation had no effect on renal peripheral benzodiazepine receptor density or affinity. The decrease in peripheral benzodiazepine receptor density was localized to the renal cortex and the outer stripe of the medulla by gross dissection of renal slices and renal tissue section autoradiography. The specific effect of adrenalectomy on renal peripheral benzodiazepine receptor density, the lack of direct effect of aldosterone on [3H] Ro 5-4864 binding and the localization of the change in peripheral benzodiazepine receptor density to the renal cortex and outer stripe suggest that these changes may reflect an adaptation of the renal nephron (possibly the distal convoluted tubule, intermediate tubule and/or the collecting duct) to the loss of mineralocorticoid hormones.

Adrenal Cortex↗
PubMed1983

Parasympathetic ganglia: naloxone antagonizes inhibition by leucine-enkephalin and GABA.

Synaptic transmission in parasympathetic ganglia of the cat urinary bladder was depressed by low doses (0.1-10 micrograms i.a.) of Leu- or Met-enkephalin but only by larger doses (10 micrograms-1 mg i.a.) of morphine. Naloxone blocked the depressant effects of the opiates as well as the depression produced by GABA, but did not block the depressant effects of norepinephrine. Intracellular recording revealed that Leu-enkephalin reduced EPSP-amplitude and lowered the probability of synaptically evoked firing without altering postsynaptic membrane potential or resistance. These findings suggest that enkephalinergic inhibition in bladder ganglia is mediated at least in part by a presynaptic site of action on delta opiate receptors.

Animals↗
PubMed1981

Morphine antagonists and consummatory behaviors.

Opiate antagonists were tested for their effects upon either drinking or eating in eight experiments. Naloxone, nalorphine, and the active isomer of WIN 44,441 all reduce drinking. Neither an analog of nalorphine that does not cross the blood-brain barrier, nor the inactive isomer of WIN 44,441 is effective in reducing water intake. These data provide support for the conclusion that these antagonists ahve stereospecific effects within the central nervous system. Naloxone suppresses drinking following procedures inducing osmotic, volemic, or hormonal thirst. Naloxone suppresses eating following procedures inducing glucoprivation but does not alter eating elicited by tail-pressure. Collectively, these data lead to the conclusion that endorphins play a role in the organization of ingestive behavior following challenges to homeostasis.

Angiotensin II↗
PubMed1981

Opiate antagonists and sexual behavior in female hamsters.

Mating or administration of morphine to female hamsters reliably decreases lateral displacement, a sensitive index of female sexual responsitivity. Morphine's effects are antagonized by naloxone. We asked whether endogenous opiates are significantly involved in the mating-induced inhibition of sexual responsitivity by testing whether naloxone or naltrexone attenuated the mating-induced decreases in lateral displacement. Naloxone (4 mg/kg) increased lateral displacement in only one of three tests in females before mating. Naloxone did not attenuate the mating-induced decreases in lateral displacement or lordosis behavior in either ovariectomized, hormonally supplemented or intact females. Large doses of naltrexone produced no reliable effects on sexual behavior during estrus in unmated females, nor did it attenuate the mating-induced decreases in sexual responding, regardless of the time of day of mating. Naloxone often increases the variability of sexual responding. We conclude that naloxone-sensitive mechanisms do not play a critical role in the expression of sexual behavior in female hamsters.

Animals↗
PubMed1980

Naloxone reduces fluid intake: effects of water and food deprivation.

Food and fluid deprived and nondeprived male rats showed 36% and 46% decreases, respectively, in sucrose consumption 15-min after injection with 2 mg/kg of naloxone in one hr tests. The magnitude of this decrease was not correlated with an index of naloxone's ability to produce a sickness, as measured by the conditioned taste aversion test. Tests with animals scheduled to drink water in a 15-min daily session showed naloxone had similar effects in reducing water intake in 23-hr and 47-hr water deprived rats. Morphine, when self-administered, produced an increase in water intake during 6-hr sessions. The data support the idea that naloxone disrupts a component of normal regulation of ingestion.

Animals↗
PubMed1979

Morphine and naloxone's effects on sexual behavior of the female golden hamster.

The effects of morphine and naloxone were observed after administration to female golden hamsters (Mesocricetus auratus). Large doses of morphine, 80 mg/kg, consistently produced sedation and behavioral depression of responses to nociceptive stimuli. Smaller doses of morphine (e.g., 10 mg/kg), that produced few other behavioral changes, suppressed a measure of female sexual responding. The suppressive effects on sexual behavior were reversed by 4 mg/kg of naloxone. Morphine administered intracerebroventricularly had little effect on sexual responding, even at doses which produced other side effects. Doses of 4 and 8 mg/kg of naloxone in opioid-naive subjects did not reliably alter sexual responding up to 2 hr after administration. These observations lead to the suggestion that morphine produces effects which are incompatible with full sexual functioning in female hamsters.

Animals↗
PubMedDate not supplied

The effects of low doses of morphine on the activity of dopamine-containing cells and on behavior.

Intravenous (IV) administration of 10 ug/kg of morphine sulfate increased the firing rate of Type A dopamine neurons but decreased the extracellular activity of Type B dopamine cells in the substantia nigra pars compacta and ventral tegmental area of anesthetized male rats. The morphine-produced increase in Type A cells was antagonized by 0.10 mg/kg of naloxone, whereas the suppression of B cells was blocked only by pretreatment with 5.0 mg/kg of naloxone. This same low dose of morphine (IV) also produced increased locomotor activity in awake male rats within 10 min of administration.

Animals↗