Circulating atrial natriuretic peptides in conscious rats: regulation of release by multiple factors.

Cardiocytes in the atria contain a prohormone that gives rise to atrial natriuretic peptides (ANP's), which have intrinsic hemodynamic regulatory activity. The distribution of ANP's in the brain suggests the involvement of these peptides in central cardiovascular regulation. In conscious rats with chronic indwelling catheters, volume loading with isotonic saline or glucose increased the amount of circulating immunoreactive ANP's by a factor of 4 to 5, as determined by radioimmunoassay. Hyperosmotic challenge with a hypertonic NaCl solution or anesthesia with halothane caused similar increases in plasma ANP's. Results obtained with the denervated-heart preparation indicate that neuronal influences are important in the release of ANP's induced by volume loading. As judged from reversed-phase high-performance liquid chromatography of extracted plasma and radioimmunoassay of collected fractions, the circulating physiologically important ANP's in the conscious rodent appear to be alpha-rANP(5-28) (atriopeptin III) and either alpha-rANP(3-28) [ANF(8-33)] or alpha-rANP(1-28) (ANF).

Methionine and leucine enkephalin in rat neurohypophysis: different responses to osmotic stimuli and T2 toxin.

Specific radioimmunoassays were used to measure the effects of hypertonic saline (salt loading), water deprivation, and trichothecene mycotoxin (T2 toxin) on the content of methionine enkephalin (ME), leucine enkephalin (LE), alpha-neoendorphin, dynorphin A, dynorphin B, vasopressin, and oxytocin in the rat posterior pituitary. Concentrations of vasopressin and oxytocin decreased in response to both osmotic stimuli and treatment with T2 toxin, but the decrease was greater with osmotic stimulations. Similarly, concentrations of LE and dynorphin-related peptides declined after salt loading and water deprivation; LE concentrations also decreased after treatment with T2 toxin. The concentration of ME decreased after water deprivation, did not change after salt loading, and increased after T2 toxin treatment. The differentiating effects of these stimuli on the content of immunoreactive LE and ME are consistent with the hypothesis that LE and ME may be localized in separate populations of nerve endings with different roles in the posterior pituitary.

On the origin of Leu-enkephalin and Met-enkephalin in the rat neurohypophysis.

The posterior lobe of the pituitary contains large amounts of Leu- and Met-enkephalin (LE and ME, respectively). A marked depletion of ME (81.9%) and LE (94.5%) in the posterior pituitary occurred after transection of the pituitary stalk. This indicates that most, if not all, of the enkephalins are in processes of central neurons. In the present study, I attempted to determine the source(s) of the LE- and ME-containing fibers in the posterior pituitary by examining the effects of hypothalamic lesions or fiber transections on the LE and ME levels. Lesions of the hypothalamic paraventricular nuclei caused ME and LE levels in the posterior pituitary to decrease significantly (55.6% and 27.6%, respectively). Deafferentation of the medial basal hypothalamus (creating islands of tissue containing the ventromedial and arcuate nuclei) resulted in a marked reduction in LE (94.1%) and ME (54.7%). Treating neonatal rats with monosodium glutamate resulted in a selective destruction of arcuate nucleus neurons, but did not affect LE and ME concentrations in the posterior pituitary. Thus, about half of the ME in the posterior pituitary seems to be provided by neurons in the vicinity of the paraventricular and ventromedial nuclei, whereas only about one quarter of the LE in the posterior pituitary is in processes of the paraventricular nucleus neurons. The remainder of the LE is contributed to the posterior pituitary by neurons outside the medial basal hypothalamus, probably by the supraoptic nucleus neurons. These findings are consistent with the hypothesis that LE and ME may be localized in separate populations of nerve endings in the neurohypophysis and may have different roles.

Opioid-mediated cardiovascular effects of clonidine in spontaneously hypertensive rats: elimination by neonatal treatment with monosodium glutamate.

The interaction between clonidine and opiate receptor antagonists on arterial blood pressure (BP) and heart rate were examined in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). In conscious SHR, the hypotension and bradycardia caused by clonidine, 5 micrograms/kg iv, were significantly attenuated by naltrexone, 2 mg/kg ip. In urethane-anesthetized SHR, the reduction in mean BP and heart rate in response to 5 nmol clonidine microinjected into the nucleus of the solitary tract (NTS), were similarly inhibited after intra-NTS microinjection of 100 ng DL-naloxone but not after the same dose of D-naloxone. Neonatal treatment of SHR by monosodium glutamate (MSG) markedly reduced the beta-endorphin (BE) but not the leucin-enkephalin content of the arcuate nucleus and the NTS. MSG treatment did not affect the basal BP of these animals, but significantly reduced the hypotensive effect of clonidine and eliminated its susceptibility to opiate antagonists in both conscious and anesthetized SHR. In conscious and anesthetized WKY, the cardiovascular effects of clonidine were smaller than in SHR and were unaffected by naloxone or naltrexone. Neonatal treatment of WKY with MSG reduced the BE content of the arcuate nucleus but not of the NTS. MSG treatment of WKY did not influence either basal BP or the cardiovascular effects of clonidine, and the latter remained unaffected by opiate antagonists. These findings support the hypothesis that in SHR, but not in WKY, the centrally mediated cardiovascular effects of clonidine are partially mediated by the release of a BE-like opioid. They also strongly suggest that the site of both the release and the action of this opioid is in the NTS.

Stress-induced secretion of adrenocorticotropin, corticosterone, and prolactin in experimentally and genetically hypertensive rats.

Plasma levels of immunoreactive ACTH, corticosterone (CS), and PRL in two-kidney, one clip (2K1C) hypertensive SABRA, hypertension-prone (SBH), hypertension-resistant (SBN), and normotensive SABRA rats were compared under both quiescent conditions and after acute (2 min) cold water stress. Serum levels of CS were higher in 2K1C hypertensive compared with normotensive SABRA rats under both quiescent and stressful conditions. Circulating levels of ACTH and PRL were similar in both groups under quiescent conditions. Resting circulating levels of CS were higher in the SBH rats compared with SABRA or SBN rats. Serum PRL levels were similar in SBH and SABRA rats under both quiescent and stressful conditions. Resting PRL levels in the SBN rats were lower compared with the SABRA rats. Resting serum levels of ACTH and CS in the SBN rats were similar to those found in the SABRA rats. After stress exposure serum ACTH and CS levels were elevated in all groups. Serum PRL levels in SBN rats were not affected by stress, unlike the marked elevation seen in the other groups. Our study demonstrates increased secretion of CS in both 2K1C hypertensive and SBH rats under quiescent conditions. Both 2K1C hypertensive and SBH rats have normal hormonal capacity to respond to stress. SBN rats exhibited reduced PRL secretion under both quiescent and stressful conditions. It is suggested that abnormal activity of the hypothalamic-pituitary-adrenal system may play a role in the pathogenesis of 2K1C and genetic hypertension as well as in resistance to hypertension.

Ontogeny and regional distribution of proenkephalin- and prodynorphin-derived peptides and opioid receptors in rat hippocampus.

Levels of prodynorphin- and proenkephalin-derived peptides were determined in whole hippocampus of prenatal and early postnatal rats and in five regions of the hippocampus of the adult rat. Using autoradiography, opioid receptor subtypes were localized in coronal sections of adult hippocampus. The opioid peptides are present in very low concentrations in prenatal hippocampus, with only dynorphin B and alpha-neo-endorphin being present in significant amounts. The main increase in concentrations of the opioid peptides occur between day 7 and 14 postnatally, when dynorphin A, dynorphin A-(1-8), dynorphin B and alpha-neo-endorphin reach their adult levels. beta-Neo-endorphin and [Met]enkephalyl-Arg-Gly-Leu do not reach their maximal level until later in development. There is a distinct differential distribution of the opioid peptides in the subregions of the hippocampus; the subiculum and CA1 are relatively poor in prodynorphin-derived peptides but do contain significant amounts of [Met]enkephalin and [Leu]enkephalin. Very high concentrations of dynorphin B and alpha-neo-endorphin are present in region CA4. Dynorphin A-(1-8) and [Met]enkephalin have their highest concentrations in the dentate gyrus. There is a 5-fold higher concentration of [Met]enkephalin in the ventral hippocampus compared to the dorsal hippocampus. A similar trend is seen with dynorphin A-(1-8) but not with the other opioid peptides. The most abundant opioid receptor population in the hippocampus is of the mu type and it is densest in and around stratum pyramidale of the region CA3. There are relatively few kappa opioid receptors in the rat hippocampus. These results indicate the presence of at least two independent opioid neuronal systems (enkephalin and dynorphin) in rat hippocampus and the presence of mu-, delta- and kappa-opioid receptor subtypes.

Distribution of atrial natriuretic factor-like immunoreactive neurons in the rat brain.

Using antisera generated in rabbits against rat atriopeptin III [alpha-rANP(5-28)] and human alpha-atrial natriuretic polypeptide we mapped the distribution of atrial natriuretic factor-like immunoreactivity throughout the rat central nervous system. Cell bodies were observed in the telencephalon (nucleus interstitialis striae terminalis and between the amygdala centralis and medialis), throughout the diencephalon in all nuclei of the "anteroventral third ventricle", the base of the hypothalamus, the subzona incerta area, the medial forebrain bundle and the medial habenula, in the mesencephalon (mamillary body, substantia nigra lateralis, dorsal and ventral parabrachial nuclei) and very sparse in the medulla oblongata along the fourth ventricle towards the vestibular nuclei, the nucleus tractus solitarii and nervi trigemini. Fibers were present wherever cell bodies were located. The highest relative densities were observed in the anteroventral third ventricle area and the medial habenula. Sparse fibers were also seen in the spinal cord (dorsal and ventral horn and around the central canal) and in the posterior pituitary. The predominance of the atrial natriuretic factor-like perikarya and fibers in the anteroventral third ventricle area suggests an involvement of this peptide in central blood pressure control.

The distribution of melanin-concentrating hormone-like immunoreactivity in the central nervous system of rat, guinea-pig, pig and man.

The distribution of melanin-concentrating hormone-like immunoreactivity was investigated by radioimmunoassay in the CNS of rat, guinea-pig, pig and man. Highest concentrations of melanin-concentrating hormone-like immunoreactivity were found in the hypothalamus of all the species: rat 204.4 +/- 14.9; guinea-pig 159.5 +/- 23.3; pig 10.9 +/- 4.5 and man 80.1 +/- 19.1 pmol/g. Gel chromatographic analysis of hypothalamic extracts showed five immunoreactive peaks of melanin-concentrating hormone-like immunoreactivity in the rat and pig and six in the guinea-pig and man. High-performance liquid chromatography analysis of hypothalamic extracts showed five immunoreactive peaks in rat, guinea-pig, pig and four in man. However, these peaks appeared at different retention times from that of the single peak of salmon melanin-concentrating hormone. Examination of subcellular fractions of whole rat brain showed that most of the melanin-concentrating hormone-like immunoreactivity is found in the synaptosome fraction. Stimulation of melanin-concentrating hormone-like immunoreactivity release from rat hypothalamic slices revealed that potassium in the presence of calcium stimulated melanin-concentrating hormone-like immunoreactivity release. These findings suggest that mammalian melanin-concentrating hormone-like immunoreactivity has a different amino acid sequence from salmon melanin-concentrating hormone and may exist in multiple molecular forms. It is possible that melanin-concentrating hormone may play a role as a neurotransmitter or modulator in the mammalian CNS.

The hypertensinogenic activity of 18,19-dihydroxycorticosterone in adrenalectomized rats.

Adrenalectomized, spontaneously hypertensive rats (SHR) were used to test the hypertensinogenic property of recently synthesized 18,19-dihydroxycorticosterone (18,19-Di-OH-B). The steroid was given via Alzet miniosmotic pump, with and without aldosterone. Neither 18,19-Di-OH-B (5 micrograms) nor aldosterone (5 micrograms) increased blood pressure in SHR when given alone; when administered together they resulted in a significant rise in blood pressure. Results indicate a high probability that certain mineralocorticoids, which are inactive by themselves, might play a role in the etiology of hypertension when acting together under physiological conditions.

Environmentally-induced modification of the benzodiazepine/GABA receptor coupled chloride ionophore.

The benzodiazepine/GABA receptor coupled chloride ionophore was examined in brain membranes of rats maintained in either a conventional animal facility or a "protected" (low-stress) environment. Following a 10 min ambient temperature swim, animals maintained in both environments had qualitatively similar increases in the number (Bmax) of [35S]t-butylbicyclophosphorothionate (TBPS) binding sites, the apparent affinity of this radioligand, and the efficacy and potency of Cl- to enhance [3H]flunitrazepam binding. Nonetheless, the Bmax of [35S]TBPS and efficacy of Cl- to enhance [3H]flunitrazepam binding were significantly lower in animals housed in the protected environment compared to those maintained in a conventional facility both before and after swim stress. Furthermore, in rats housed in a protected environment, sequential removal of animals from a common cage (cohort removal), produced a very rapid increase (less than or equal to 15 s) in Cl(-)-enhanced [3H]flunitrazepam binding in cortical and hippocampal but not cerebellar membranes. Cohort removal also produced a sequential increase in the number of [35S]TBPS binding sites and apparent affinity of this radioligand in cerebral cortical membranes. The effects of cohort removal were not observed in animals subjected to ambient temperature swim or if animals were removed from different cages. Changes in the benzodiazepine/GABA receptor coupled chloride ionophore produced by cohort removal from a common cage preceded any statistically significant changes in circulating levels of alpha-MSH, beta-endorphin, ACTH or corticosterone. These findings suggest that the benzodiazepine/GABA receptor chloride ionophore complex (supramolecular complex) is under both tonic and acute regulation by the environment, and may subserve a physiologically relevant function in the response to stressful or anxiety producing stimuli.

The relationship between cardiovascular and pain regulatory systems.

An increasing amount of anatomical, physiological, and pharmacological evidence suggest that pain inhibitory circuitry is linked with cardiovascular regulatory systems in man and laboratory animals. Induction of hypertension in rats by different methods (mineralocorticoid treatment, stenosis of renal artery, or social deprivation) is associated with reduced responsiveness to noxious thermal stimuli (hot-plate) or to noxious mechanical stimuli (paw pressure). Genetically hypertension-prone rats derived from the SABRA strain and spontaneously hypertensive rats derived from Wistar/Kyoto strain also display a similar hypoalgesia. Acute increases in blood pressure are associated with reduced sensitivity to painful stimuli. Additionally, the interaction between blood pressure and pain perception has also been supported by the demonstration that various experimental interventions that diminish the magnitude of hypertension also attenuate the hypoalgesia. Recent clinical findings are also in agreement with the laboratory animal findings since sensory and pain thresholds have been shown to be significantly higher in unmedicated essential hypertensive subjects compared to normotensive controls. Thus, the human data corroborate animal data and suggest that a relation between blood pressure and pain sensitivity is likely to be a general phenomenon. It is unlikely that damage to peripheral pain fibers caused by a change in blood pressure contributes to the observed hypoalgesia. Naloxone, which has no effect on blood pressure, returns the pain sensitivity to normal levels. Behavioral tests (open field and motor activity cage) of normotensive and of renal and genetically (SBH and SHR) hypertensive rats exclude the possibility of a general motor deficit in hypertensive rats. Endogenous opioid peptides in central and peripheral nervous systems as well as in endocrine organs are implicated, although non-opioid mechanisms are also evident. Activation of baroreceptor afferents by acute or chronic increases in arterial or venous blood pressure may play an important role in the somatosensory responses associated with the increase in blood pressure. Coordinated cardiovascular-pain regulatory responses may be part of an adaptive mechanism that helps the body to face stressful events.

Corticotropin releasing factor-like immunoreactivity in sensory ganglia and capsaicin sensitive neurons of the rat central nervous system: colocalization with other neuropeptides.

Immunohistochemistry and radioimmunoassay (RIA) revealed that corticotropin releasing factor (CRF)-like immunoreactivity was found to be colocalized with substance P (SP)-, somatostatin (SST)- and leu-enkephalin (LENK)-like immunoreactivity in the dorsal root- and trigeminal ganglia, the dorsal horn of the spinal cord (laminae I and II), the substantia gelatinosa, and at the lateral border of the spinal nucleus and in the tractus spinalis of the trigeminal nerve. These peptides were also located in fast blue labeled cells of the trigeminal ganglion following injection of the dye into the spinal trigeminal area. This indicates that there are possible sensory projections of these peptides into the spinal trigeminal area. Capsaicin treatment of neonatal rats resulted in a marked decrease in the density of CRF-, SP-, VIP- and CCK-containing neurons in the above mentioned hindbrain areas, whereas SST- and LENK-immunoreactivity were not changed. RIA revealed that, compared to controls, CRF, SP and VIP concentrations in these areas were decreased in rats pretreated with capsaicin, while SST levels were increased; CCK and LENK levels were unchanged. It is concluded that the primary afferent neurons of the nucleus and tractus spinalis of the trigeminal nerve are richly endowed with a number of peptides some of which are sensitive to capsaicin action. The close anatomical proximity of these peptide containing neurons suggests the possibility of a coexistance of one or more of these substances.

Dynorphinergic pathways of Leu-enkephalin production in the rat brain.

Leu-Enkephalin (LE) is an endogenous opioid peptide that can arise from two distinct precursors: proenkephalin and prodynorphin. Experiments were designed to differentiate LE derived from proenkephalin versus that derived from prodynorphin. The most dense collections of dynorphin-positive fibers and terminals are in the substantia nigra and posterior pituitary, areas rich in dynorphin-related peptides. The concentration of LE in these regions is significantly higher than that of ME-Arg-Gly-Leu; the ratio of LE to ME-Arg-Gly-Leu is therefore greater than that found in the proenkephalin precursor, which is unity. Globus pallidus deafferentation resulted in a significant decrease of dynorphin B and LE, but not ME-Arg-Gly-Leu, in the substantia nigra. Mild intermittent foot shock (0.2 mA, 20 min) causes a significant increase of dynorphin B and LE in the substantia nigra, but has no effect on ME-Arg-Gly-Leu concentrations. Thus, in the substantia nigra LE may be derived primarily from prodynorphin. Likewise, in the posterior pituitary, osmotic stimulus (e.g., 2% NaCl as drinking fluid) causes marked depletion in dynorphin and LE but has no effect on ME levels suggesting that in the posterior pituitary LE is derived primarily from dynorphin.

Localization and quantitation of proenkephalin-derived neuropeptides in the rat hippocampus.

We have measured the content of met- and leu-enkephalin and dynorphin B in the rat hippocampus, and localized these opioid peptides within the intrinsic hippocampal neuronal circuitry with specific lesions. Several enkephalins, two of which were shown to be met- and leu-enkephalin, were identified in rat hippocampus. The levels of the enkephalin-related peptides were unaffected by intrahippocampal injections of colchicine, which destroyed the great majority of the hippocampal granule cells, while the level of dynorphin B, which serves as a marker for the proenkephalin B-derived peptides, was markedly depleted. Entorhinal cortical lesions ablating the perforant pathway input to the hippocampus did not significantly alter dynorphin B nor enkephalin levels in the hippocampus. Unilateral fimbrial transection caused a small but significant increase in dynorphin B on the side of the lesion relative to the non-lesioned side, although neither side was significantly different from control, while at the same time causing a significant bilateral increase in both met- and leu-enkephalin levels. This may result from loss of a direct or indirect stimulatory input to peptide-containing neurons within the hippocampus. The enkephalins appear to be located in neuronal cell bodies intrinsic to the body of the hippocampus, while the dynorphins are likely to be intrinsic only to the granule cell-mossy fiber system originating in the dentate gyrus.

On the origin of dynorphin A and alpha-neo-endorphin in the substantia nigra.

The substantia nigra contains among the highest dynorphin A (Dyn A) and alpha-neo-endorphin (alpha-Neo) concentrations in the central nervous system. No dynorphin positive cell bodies are found there, only a dense network of nerve fibers and terminals. The present study provides evidence that the Dyn A and alpha-Neo in the substantia nigra are in neural processes arising from cells located in the head of the caudate nucleus. This neuronal system has been characterized by assaying Dyn A and alpha-Neo in the substantia nigra after a number of surgical transections of neuronal pathways in the rat forebrain and midbrain. Fibers containing dynorphins and neo-endorphins seem to pass through the internal capsule, ansa lenticularis, and medial forebrain bundle on their way from the striatum to the substantia nigra.

Altered pain perception in hypertensive humans.

Sensory and pain thresholds to electrical stimulation of tooth pulps were measured in normotensive and essential hypertensive unmedicated human subjects. In both adult and young subjects there was a significant correlation between blood pressure and pain sensitivity: hypertensives had a higher threshold for sensation of pain in the tooth-pulp test than normotensive controls. An interrelationship between blood pressure and pain regulation is suggested.

Opiate receptor binding in the brain of the hypertensive rat.

Experimental and genetic hypertension in male rate is accompanied by a lower specific [3H]naloxone binding in the dorsal horn of the spinal cord, and in the hippocampus as compared to controls. Rats which are genetically resistant to hypertensive stimuli have a higher specific [3H]naloxone binding in the nucleus tractus solitarius and lower opiate receptor binding in the dorsal horn. Together with previous studies which demonstrated a correlation between blood pressure and pain sensitivity, these results support the notion that specific brain loci participate in co-regulation of pain perception and blood pressure.

Pain sensitivity and opioid activity in genetically and experimentally hypertensive rats.

Pain sensitivity was studied in renal and DOCA-salt hypertensive rats, and in two strains of rats derived from the same parental strain for their sensitivity (H) or immunity (N) to hypertension induced by DOCA-salt treatment. Experimentally hypertensive rats, and H and N rats were less sensitive to painful stimuli than their appropriate controls, as assessed in the hot-plate and paw pinch tests. Naloxone reversed this hypoalgesia in both experimentally and genetically hypertensive rats while it did not affect blood pressure in any rat-type tested. Opioid activity was measured with the radioreceptor assay in several brain regions and pituitary gland of both experimentally and genetically hypertensive rats. Experimentally hypertensive rats had a 45% higher level of opioid activity in the spinal cord compared to control. Rats of the H and N strains both exhibited higher levels of opioid activity in the spinal cord, hypothalamus and pituitary. It is suggested that control systems for blood pressure and pain sensitivity are closely associated in the rat.

Distribution of immunoreactive Met-enkephalin-Arg6-Gly7-Leu8 and Leu-enkephalin in discrete regions of the rat brain.

The distribution of immunoreactive (ir) leucine-enkephalin (LE) and ir-methionine-enkephalin-Arg-Gly-Leu (ME-RGL) in 101 microdissected rat brain and spinal cord regions was determined using specific and sensitive radioimmunoassays. The highest concentrations of LE and ME-RGL were measured in globus pallidus (5190 and 4378.8 fmol/mg protein, respectively). Very high concentrations of LE and ME-RGL (greater than 750 fmol/mg protein) were found in the central amygdaloid nucleus, anterior hypothalamic nucleus, lateral preoptic area, nucleus of the solitary tract (medial and commissural parts), bed nucleus of stria terminalis, dorsomedial nucleus, parabrachial nuclei, periaqueductal gray and motor hypoglossal nucleus. Very high concentrations of ME-RGL were found in 14 additional brain regions including medial preoptic area, area postrema, nucleus ambiguus, periventricular nucleus, ventromedial nucleus, interpeduncular nucleus, paraventricular, arcuate and others. High concentrations of LE (between 500 and 750 fmol/mg protein) were found in 15 brain areas, among them the periventricular nucleus, medial preoptic area, suprachiasmatic nucleus, dorsal premamillary nucleus, ventromedial nucleus, arcuate nucleus, nucleus ambiguus, locus coeruleus, substantia nigra. High concentrations of ME-RGL were measured in 13 brain areas including the suprachiasmatic nucleus, lateral septal nucleus, raphe magnus, motor facial nucleus, lateral amygdaloid nucleus, sensory trigeminal nucleus, nucleus accumbens, caudate-putamen. Moderate concentrations of LE (between 250 and 500 fmol/mg) were found in 46 brain areas such as the lateral septal nucleus, nucleus accumbens, caudate-putamen, several amygdaloid nuclei, supraoptic nucleus, the perifornical nucleus, posterior hypothalamic nucleus, red nucleus. Moderate concentrations of ME-RGL were detected in 27 areas such as the median eminence, nuclei of the reticular formation, supraoptic nucleus, red nucleus and others.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization and quantitation of dynorphin B in the rat hippocampus.

The present study measures the content of dynorphin B in the rat hippocampus, and localizes the dynorphins within the intrinsic hippocampal neuronal circuitry. The level of dynorphin B, which is representative of the prodynorphin-derived peptides, was markedly depleted by intrahippocampal injection of colchicine, which destroyed the great majority of the hippocampal granule cells and the associated mossy fiber pathway. The hippocampus contralateral to the injection demonstrated a slight, non-significant rise in dynorphin B levels after colchicine. Entorhinal cortical lesions ablating the perforant pathway input to the hippocampus did not significantly alter dynorphin B levels in the hippocampus. Unilateral fimbrial transection caused a small but significant increase in dynorphin B on the side of the lesion relative to the unlesioned side, but neither side was significantly different from control.