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J Rochford

Publications and source records attributed to J Rochford.

At least 37 records · Page 2Linked to original sources
PubMed1995

Dissociation between behavioral and hormonal responses to the forced swim stress in lactating rats.

Retention of immobility in the Porsolt forced swim test is believed to be dependent upon glucocorticoid secretion in male rats. Because lactating females exhibit increased basal glucocorticoid secretion and blunted stress responses, we tested the hypothesis that lactation-induced changes in adrenal glucocorticoid and in circulating estrogen and progesterone levels would improve retention and/or acquisition of immobility. Immobility was recorded during 3 intervals of 5 min on day 1 (acquisition) and one 5 min interval 24 h later (retention). Blood samples were collected before the swim test and at various times after the onset of stress for plasma ACTH and corticosterone (B) determinations. Male rats (young=200 g, old=325 g) were compared to virgin females (V) and to lactating females in early (day 8-10, EL) and late (day 17-19, LL) lactation. Adrenalectomy (ADX) and ovariectomy (OVX) were performed 5 and 10 days prior to testing, respectively. All animals acquired immobility at the end of the 15 min swim on day 1, but only the young male group exhibited a significant retention of immobility on day 2. Total immobility was higher in males than females (V) although basal and stress-induced ACTH and B secretion were comparable on both testing days. Lactational status did not affect immobility in either the acquisition or retention phases. However, stress-induced ACTH secretion was greatly diminished in intact and ADX lactating females (EL and LL) compared to virgins (LL < EL < virgin), demonstrating a clear dissociation between behavioral and neuroendocrine responses. Following ADX, immobility in the retention phase was either decreased in males or increased in lactating females. Finally, OVX decreased immobility in both lactating (EL) and virgin females without significantly altering the magnitude of the ACTH and B responses to stress. In summary, our results demonstrated both sex-related and lactation-related differences in the behavioral and endocrine responses to he forced swim test of Porsolt. Although retention of the immobile response is thought to involve glucocorticoids and/or opioids secreted during the first testing session, we did not find evidence for a direct relationship between basal or stress-induced total corticosterone secretion, the magnitude of ACTH response to stress and behavioral scores in the retention period. However, experimental variables such as body weight, sex and water depth could significantly modify the outcome of behavioral testing and question the validity of glucocorticoid-mediated retention processes. Since the effect of ADX was reversed in lactating females compared to male rats, we hypothesize that glucocorticoid sensitivity of cognitive processes controlling behavioral reactivity is different from that controlling hypothalamic-adrenocortical function. Our results also demonstrated a clear dissociation between behavioral and neuroendocrine responses to the swim test, in particular during lactation. In early and late lactation, blunted responsiveness to stress was not caused by enhanced glucocorticoid feedback but might result from modifications in the inhibitory and/or stimulatory inputs to hypothalamic neurons controlling adrenocortical activity.

Adrenalectomy↗
PubMed1994

The interaction between prenatal stress and neonatal handling on nociceptive response latencies in male and female rats.

Neonatal handling produces physiological and behavioral changes that persist into adulthood. These effects are opposite to those resulting from prenatal stress (PS). We examined the interaction between PS and handling on nociception in adult male and female rats. Randomly selected pregnant rats were subjected to restraint stress on days 13-17 of gestation for 25 min each day, or left undisturbed. At birth, selected stressed/nonstressed litters were assigned to be handled. handling consisted of 15 min of separation from the dam, once per day, from postnatal days 1-14. At 4 months of age, rats were placed on a 50 degrees C hot plate, and their latencies to paw lick were recorded. Prenatal stress and handling interacted to affect latencies in male rats. Handled (H)/PS rats had significantly lower paw lick latencies than nonhandled (NH)/PS rats (p < 0.05). However, handling had no effect on the male offspring of control dams. Handling elevated paw lick latencies in the female offspring of control dams, an effect that was most pronounced in diestrous vs. estrous rats. The NH/PS rats showed significantly elevated latencies compared to NH/NS rats (p < 0.05). These results suggest that handling effects on nociception are most apparent in rats subjected to PS; in males at least, these effects would otherwise not be present.

Adrenocorticotropic Hormone↗
PubMed1993

Male rats classified as copulators and noncopulators respond differentially on the hot plate test.

Sexually naive male rats that fail to copulate with a sexually receptive female (noncopulators) have been shown to be less responsive to a variety of environmental stimuli in comparison to rats that do engage in copulation (copulators). In this experiment, it was found that noncopulators were less responsive than copulators to noxious thermal stimulation as determined by their latency to paw lick on a 50 degrees C hot plate. Pain sensitivity was not influenced in either noncopulators or copulators by exposure to a sexually receptive female. These results add to the list of differences between copulators and noncopulators.

Animals↗
PubMed1993

Effect of naloxone on the habituation of novelty-induced hypoalgesia: the collateral inhibition hypothesis revisited.

Repeated daily administration of the opiate receptor antagonist naloxone prior to hotplate tests provokes longer paw-lick latencies by attenuating the habituation of novelty-induced hypoalgesia. This hypoalgesia has been found to persist when pain tests are subsequently conducted following saline administration. The present experiments were conducted to determine whether the substrates mediating the hypoalgesia observed during naloxone and saline tests are similar or distinct. Neither the hypoalgesia observed during naloxone nor saline tests were affected by the induction of tolerance to the hypoalgesic effect of morphine, suggesting that both effects are mediated by nonopioid antinociceptive mechanisms. Previous work from our laboratory demonstrated that the hypoalgesia observed during naloxone tests is inhibited by clonidine, enhanced by yohimbine, and unaffected by prazosin and phentolamine. In the present article, we report a similar pattern of results for the hypoalgesia observed during saline tests. It is concluded that the substrates mediating both effects are similar. The results are discussed in relation to the possibility that an opioid substrate involved in habituative learning may be inhibitory on a nonopioid antinociceptive substrate.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1993

Naloxone potentiation of novelty-induced hypoalgesia: characterization of the alpha-noradrenergic receptor subtype.

Repeated daily administration of the opiate receptor antagonist naloxone (10 mg/kg) attenuates the habituation of novelty-induced hypoalgesia. This effect can be reversed by the alpha 2-noradrenergic receptor agonist clonidine and enhanced by the alpha 2-antagonist yohimbine. The present experiments were conducted to provide further support for the importance of the alpha 2-receptor and determine the possible influence of the alpha 1-receptor. Naloxone's effect on novelty-induced hypoalgesia was not affected by pretreatment with the specific alpha 1-receptor antagonist prazosin (0.2-1.0 mg/kg, SC) or the nonselective alpha antagonist phentolamine (2.0-10.0 mg/kg). In a second series of experiments, it was found that the potentiation of naloxone's effect by yohimbine (2 mg/kg) was reversed by clonidine (0.1 mg/kg) but was not influenced by prazosin or phentolamine. These results suggest that the alpha 1-noradrenergic receptor subtype does not mediate the effect of naloxone on novelty-induced hypoalgesia. They also reinforce the importance of the alpha 2-receptor subtype in the mediation of this effect.

Animals↗
PubMed1992

Clonidine and yohimbine modulate the effects of naloxone on novelty-induced hypoalgesia.

Previous research has shown that repeated daily pretreatment with the opiate receptor blocker naloxone retards the development of habituation to novelty-induced hypoalgesia. The present experiments were conducted in order to determine whether noradrenergic substrates mediates this effect. Animals in the NAL condition were administered 10 mg/kg naloxone prior to assessment of pain sensitivity on a 48.5 degrees C hot plate. Control animals (SAL condition) were administered saline prior to pain assessment, and naloxone 2-4 h later. Paw lick latencies declined over repeated tests in SAL animals, suggesting the habituation of novelty hypoalgesia. Naloxone pretreatment attenuated this decline. The longer paw lick latencies observed in NAL condition animals were reduced by administration of 2 microgram/kg clonidine, a specific noradrenergic alpha-2 receptor agonist, and enhanced in a dose dependent (0.5-4.0 mg/kg) fashion by the alpha-2 antagonist yohimbine. Clonidine and yohimbine either failed to alter pain reactivity in control animals, or produced less marked effects than those observed in naloxone-exposed animals. These results suggest that noradrenergic substrates mediate naloxone's effects on novelty hypoalgesia.

Animals↗
PubMed1992

Spinal cord alpha-2 noradrenergic receptors mediate conditioned analgesia.

The present experiment investigated the effects of direct spinal administration of the monoaminergic receptor blockers yohimbine, phentolamine and methysergide on the expression of conditioned analgesia. Animals in the Paired group received classical conditioning trials in which one context was paired with footshock administration (1 mA shock for 15 s). Animals in the Unpaired control group were administered shock in a second, different, context. On the test day animals within each condition were administered saline (20 microliters), yohimbine (30 micrograms), phentolamine (30 micrograms), or methysergide (30 micrograms) prior to receiving a hot plate test (50 degrees C) in the context previously used to shock the Paired group. These ligands were administered into the spinal fluid through a chronic, indwelling spinal catheter. Animals in the Paired group which received saline displayed longer paw lick latencies than saline-treated animals in the Unpaired group. Yohimbine, but not phentolamine or methysergide, attenuated this conditioned analgesia. These results suggest that spinal cord noradrenergic substrates mediate conditioned analgesia, and that this mediation occurs specifically through the alpha-2 noradrenergic receptor.

Analgesia↗
PubMed1992

Naloxone-induced hypoalgesia: lack of involvement of the GABA-benzodiazepine receptor complex.

Previous evidence has demonstrated that repeated daily administration of the opiate receptor antagonist naloxone prior to assessment of pain sensitivity provokes the development of a nonopioid form of hypoalgesia. The present experiments assessed whether the GABA-benzodiazepine receptor complex may be involved in the mediation of this effect. Male Wistar rats were administered 10 mg/kg naloxone prior to hot-plate tests (48.5 degrees C) for pain sensitivity for 8 consecutive days. Control animals were administered saline prior to, and naloxone 2-4 h after, assessment of pain reactivity. Beginning on the fourth or fifth day of this regimen, animals tested under the influence of naloxone displayed longer paw-lick latencies than controls. Preadministration of the GABAA agonist muscimol (1.0-5.0 mg/kg) and GABAA antagonist bicuculline (0.25-1.0 mg/kg) failed to affect paw-lick latencies in naloxone-tested and control rats. The GABAB receptor agonist baclofen (1.0-5.0 mg/kg) and the benzodiazepine receptor agonist diazepam (1.0-5.0 mg/kg) both elevated paw-lick latencies to the same degree in both groups of animals. These results suggest that the GABA-benzodiazepine receptor complex is not involved in the mediation of naloxone-induced hypoalgesia.

Analgesia↗
PubMed1991

Intrathecal administration of dynorphin A and its fragments increase heart rate and arterial pressure in the urethane anesthetized rat: mediation by a nonopioid mechanism.

Intrathecal administration of 6.50 nmol of dynorphin A (dyn A) (1-13) and (1-17) to the ninth thoracic (T9) spinal segment provoked a transient (5-10 min) increased in heart rate (40-60 beats per minute (bpm] and arterial pressure (20-25 mmHg). Intravenous administration and administration to the second thoracic (T2) segment failed to mimic the effect of T9 administration, suggesting that the cardiovascular effects of T9 administration did not occur via diffusion to the periphery or to the brainstem. The cardioacceleratory and hypertensive responses to T9 dyn A (1-13) administration were prevented by pretreatment with the nicotinic ganglion blocker hexamethonium (10 mg/kg), but were unaffected by bilateral adrenalectomy. These results suggest that the cardiovascular effects of dyn A were mediated predominantly via a sympathetic pathway that does not innervate the adrenal glands. The effects were not antagonized by pretreatment with the opiate receptor antagonist naloxone or by the specific kappa opiate receptor antagonist nor-binaltorphimine, suggesting that they were not mediated via activation of kappa opiate receptors. Further support for this conclusion was provided by experiments demonstrating that dyn A (3-13) (30 nmol), a dynorphin fragment which is devoid of kappa activity, mimicked the effect of dyn A (1-13), whereas administration of the synthetic kappa agonist U50, 488H (100 nmol), failed to elicit effects similar to those provoked by dyn A (1-13). It is concluded that the cardiovascular effects of intrathecal dyn A administration are mediated via a nonopioid mechanism.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Intrathecal administration of delta receptor agonists in the urethane anesthetized rat provokes an increase in arterial pressure via a non-opioid mechanism.

Intrathecal administration of the delta receptor specific agonists Leu5-enkephalin (Leu-Enk; 300 nmol), Met5-enkephalin (Met-Enk; 300 nmol) and [D-Pen2,D-Pen5]enkephalin (DPDPE; 100 nmol) to the T2 or the T9 segment of the rat spinal cord provoked a transient (less than 5 min) increase (15-20 mm Hg) in arterial pressure. DPDPE, but not Leu-Enk or Met-Enk, also significantly increased heart rate by 30-35 bpm. Intravenous administration of 300 nmol of Leu-Enk mimicked the effects observed following intrathecal administration. The hypertensive effect of intrathecal and intravenous Leu-Enk administration was blocked by prior systemic administration (10 mg/kg) of the nicotinic ganglion blocker hexamethonium, suggesting that the effect was mediated via sympathetic activation. The increase in arterial pressure observed following intrathecal Leu-Enk administration was not blocked by either intrathecal (305 nmol) or intravenous (10 mg/kg) administration of the opiate receptor blocker naloxone, although naloxone did block the hypertension provoked by intravenous Leu-Enk administration. Moreover, intrathecal administration of Des-Tyr1-Leu-Enk (300 nmol), an enkephalin fragment devoid of opiate receptor activity, also increased arterial pressure. These results suggest that the hypertension elicited by intrathecal delta agonist administration was not mediated via an opioid mechanism.

Anesthesia↗
PubMed1990

Intrathecal administration of calcitonin gene-related peptide (CGRP) increases heart rate and decreases arterial pressure in the urethane anesthetized rat.

Intrathecal administration of CGRP (2.15-8.60 nmol) to the ninth thoracic vertebral segment of the spinal cord in the urethane anesthetized rat provoked an increase in heart rate (peak effect of 72 bpm) and a decrease in arterial pressure (maximum fall of 15 mmHg). Administration of CGRP to the T2 level (n = 10) or intravenously (n = 6) produced qualitatively and quantitatively similar effects to those observed following administration to the T9 level. The drop in pressure resulting from intrathecal administration was unaffected by prior intrathecal administration of lidocaine (250 micrograms), systemic administration of hexamethonium (5 mg/rat), bilateral vagotomy, or combined bilateral vagotomy/hexamethonium treatment. The failure of these manipulations to alter the hypotension induced by intrathecal CGRP injection suggests that this effect was caused by leakage into the periphery. The cardioacceleration elicited by intrathecal CGRP was attenuated by intrathecal lidocaine administration and by combined bilateral vagotomy/hexamethonium treatment, but not by either treatment alone. These results suggest that CGRP's tachycardic effect is mediated by a direct spinal action involving both sympathetic and parasympathetic mechanisms.

Animals↗
PubMed1988

Lack of effect of adrenal denervation on analgesia elicited by continuous and intermittent cold water swim in the rat.

The present experiment was conducted to determine if continuous and/or intermittent cold water swim analgesia is dependent upon a factor released from the adrenal medullae. Male Sprague-Dawley rats (300-350 g) underwent either bilateral adrenal denervation or sham surgery and two weeks later were exposed to continuous (3.5 m) or intermittent (10 s in, 10 s out for 6 min) swim in water at 4 degrees C. Adrenal denervation failed to affect either intermittent or continuous cold water swim analgesia. It was concluded that both types of cold water swim analgesia are independent of adrenal medullary function.

Adrenal Medulla↗
PubMed1988

Analgesia induced by continuous versus intermittent cold water swim in the rat: differential effects of intrathecal administration of phentolamine and methysergide.

Continuous cold water swim produces analgesia that is partially mediated by a noradrenergic mechanism, but is independent of both serotonergic and opioid systems. On the other hand, intermittent cold water swim elicits analgesia which is partly mediated by an opioid mechanism; the contribution of the monoamines to the production of this analgesia is not known. Therefore, the present study was done to determine whether intermittent cold water swim is also mediated by noradrenergic and/or serotonergic substrates. Prior to either continuous (3.5 min) or intermittent (10 sec in, 10 sec out for 6 min) cold water (4 degrees C) swim, male Sprague-Dawley rats (225-250 g) were administered either the noradrenergic receptor blocker phentolamine (30 micrograms), the serotonergic blocker methysergide (30 micrograms) or artificial cerebrospinal fluid to the fifth lumbar vertebral spinal level via chronic intrathecal catheters. Phentolamine significantly attenuated the analgesia resulting from both continuous and intermittent cold water swim. Methysergide attenuated intermittent cold water swim analgesia, but was without effect on continuous cold water swim analgesia. Phentolamine, but not methysergide, also attenuated continuous footshock- (2.5 mA for 3 min) induced analgesia. The similarity between the effects of phentolamine and methysergide on continuous footshock and continuous cold water swim analgesia suggests that the effects of these drugs on cold water swim analgesia are not attributable to changes in thermoregulation. These results suggest that a spinal noradrenergic mechanism is involved in the mediation of both forms of cold water swim analgesia, whereas a spinal serotonergic mechanism is involved in only intermittent cold water swim analgesia.

Animals↗
PubMed1987

Activation and expression of endogenous pain control mechanisms in rats given repeated nociceptive tests under the influence of naloxone.

In six experiments, it was found that animals administered the opiate receptor blocker naloxone prior to either hot-plate or tail-flick nociceptive tests developed reduced sensitivity to pain relative to animals tested under saline. The naloxone-induced analgesia was most pronounced following administration of 10 mg/kg naloxone, with weaker effects occurring at 0.5 and 2 mg/kg. The effect manifested itself in tests using mild (48.5 degrees hot-plate tests), but not more severe (52 degrees or 56 degrees hot-plate tests), intensities of nociceptive stimulation. The analgesia observed in animals tested under naloxone arose in part from the attenuation of the habituation of stress-induced analgesia produced by the novelty of the test apparatus, and in part from exposure to nociceptive stimulation. It appears to be mediated by a nonopiate mechanism; naloxone enhanced the analgesia produced by exposure to brief, continuous shock, but blocked the analgesia elicited by prolonged, intermittent shock (see Lewis, Cannon, & Liebeskind, 1980). We also found that administration of naloxone prior to nociceptive testing enhanced the development of conditioned autoanalgesia (as assessed by nociceptive tests conducted under saline), and that the enhanced conditioned autoanalgesia summated with the analgesic effect of morphine. The results are discussed in terms of the activation and expression of both opiate and nonopiate pain suppression mechanisms; their implications for models of situation specific morphine analgesic tolerance are discussed.

Animals↗
PubMed1987

Morphine attenuation of conditioned autoanalgesia: implications for theories of situation-specific tolerance to morphine analgesia.

The effect of morphine administration on the development of conditioned autoanalgesia was investigated in four experiments. Animals were administered either morphine or saline and then either exposed or not exposed to nociceptive stimulation. In Experiments 1, 2, and 4 the nociceptive stimulus to which animals were exposed was electric footshock, and in Experiment 3 it was thermal stimulation produced by exposure to a hot plate. It was found that morphine administration attenuated the development of conditioned autoanalgesia produced by exposure to 1-mA shock for 45 s when tests for conditioned autoanalgesia were conducted when animals were under the influence of saline or morphine (Experiments 1 and 2). Morphine also attenuated the conditioned autoanalgesia arising from exposure to 1-mA shock for 15 s, but only when the conditions for the development and expression of conditioned autoanalgesia were made optimal (Experiment 4). Morphine failed to block conditioning when animals were exposed to 2.5-mA shock for 180 s (Experiment 1). Morphine also attenuated conditioned autoanalgesia when animals were exposed to thermal stimulation (Experiment 3), with the degree of attenuation increasing as a function of the intensity of the nociceptive stimulus. The results are discussed in terms of their implications for theories of situation-specific tolerance to the analgesic effect of morphine.

Analgesia↗
PubMed1984

Differential response of plasma glucose, amino acids and nonesterified fatty acids to insulin in depressed patients.

Levels of plasma glucose, nonesterified fatty acids and total amino acids at various times after insulin administration were determined in patients with either major depressive disorder or dysthymic disorder and in normal control subjects. For the first 30 min following insulin administration, the rate of change in glucose levels was significantly less among the patients with major depressive disorder than among either the patients with dysthymic disorder or the normal control subjects. However, during the same time period, the rates of decline in nonesterified fatty acids and total amino acids were indistinguishable among the three subject groups. Therefore, the insulin resistance in terms of glucose levels that is observed in patients with major depressive disorder is not generalized to other substances affected by insulin.

Adult↗
PubMed1983

Free tryptophan response to intravenous insulin in depressed patients.

Levels of free plasma tryptophan, total plasma tryptophan, and total amino acids were determined at various times after insulin administration in patients with either major depressive disorder or dysthymic disorder and normal control subjects. Prior to insulin administration, there were no significant differences among the three groups in any of the parameters. However, following insulin, free plasma tryptophan levels fell significantly among the patients with major depressive disorder for the first 30 min, but not among normal controls. The rate of decline among the patients with dysthymic disorder was intermediate between those of the patients with major depressive disorder and normal controls. The levels of total tryptophan and amino acids following insulin did not differ significantly among the three groups.

Adult↗