Biomedical subjects

R M Sullivan

Publications and source records attributed to R M Sullivan.

At least 19 recordsLinked to original sources

PubMed1992

The role of olfactory bulb norepinephrine in early olfactory learning.

Wistar rat pups were implanted with bilateral olfactory bulb cannulas on postnatal day 5 (PN5). On PN6, pups were trained in an olfactory classical conditioning task with peppermint odor as the CS and tactile stimulation/stroking as the UCS. Pups were randomly assigned to either PAIRED, BACKWARD or ODOR-only conditions. Half the pups in each group received intrabulbar infusions of 100 microM propranolol and half received intrabulbar infusions of saline during the training session. Propranolol infusions blocked acquisition of the learned odor preference expressed by PAIRED saline-infused pups. Diffusion of the infusate was checked in additional pups by infusing [3H]NE and performing LSC analysis. Infusate concentration did not significantly differ between the anterior and posterior halves of the bulb, but were sharply lower in the olfactory peduncle and more posterior areas. The results suggest that olfactory bulb NE is critical for early olfactory learning.

Animals↗

PubMed1992

Blockade of mitral/tufted cell habituation to odors by association with reward: a preliminary note.

Association of odor and reward during the early postnatal period modifies rat pup behavioral responses and olfactory bulb neural responses to subsequent presentations of that odor. Recent evidence has shown that olfactory bulb output neurons, mitral/tufted cells, receive convergent odor and reward inputs. The present report demonstrates that contiguous odor-reward pairings prevent mitral/tufted cell habituation to the odor that normally occurs to repeated odor-only stimulation. It is hypothesized that the maintenance of olfactory bulb responses to conditioned odors during training may allow for activation of long-term memory mechanisms.

Animals↗

PubMed1991

Norepinephrine-induced plasticity and one-trial olfactory learning in neonatal rats.

The influence of norepinephrine (NE) on the acquisition of a conditioned odor preference and enhanced focal uptake of [14C]2-deoxyglucose (2-DG) within the olfactory bulb was assessed in neonatal rat pups. On postnatal day (PN) 6, pups were injected with either an NE receptor agonist (isoproterenol), NE receptor antagonist (propranolol or timolol), or saline before one-trial odor conditioning. The experimental conditioning group received a 10-min exposure to an odor (peppermint) and reinforcing tactile stimulation similar to that received from the dam. Control groups received only the odor, only the tactile stimulation, backwards presentation of the odor and tactile stimulation or neither of these stimuli. The next day, pups were either tested for an olfactory preference (Expts. 1 and 2) or assessed for differential olfactory bulb activity using the 2-DG technique (Expt. 3). The results indicate that early odor experience with either tactile stimulation or isoproterenol is sufficient to produce a learned behavioral preference and enhanced focal 2-DG uptake within the olfactory bulb. Moreover, an NE receptor blocker injected prior to training with odor and tactile stimulation blocks the acquisition of both behavioral preference and the enhanced 2-DG uptake. In Expt. 4, the effects of tactile stimulation and isoproterenol were further assessed. An odor paired with a moderate level of either of these stimuli produces learning. However, the simultaneous presentation of a moderate level of these stimuli paired with an odor does not result in an odor preference. An odor preference may be reinstated by simultaneous presentation of these stimuli, provided the level of each of these stimuli is too low to produce an odor preference when presented alone with an odor. These data suggest that exogenous NE and tactile stimulation are additive in their effect on learning. These results are discussed in terms of the neural mechanisms underlying reinforcement in infant rats.

Animals↗

PubMed1991

The amygdala. Emotions and gut functions.

Studies are reviewed that indicate that the amygdala, and its temporal lobe pathways connecting it with entorhinal cortex and hippocampus, modulates the effects of stressful conditions on the development of gastric pathology. The amygdala integrates aversive stimulus conditions with the defensive behaviors and visceral reactions seen under such circumstances. The transmitter mechanisms for these effects include dopamine, gamma-aminobutyric acid, thyrotropin-releasing hormone, neurotensin, enkephalins, and endorphins. Recording data also show that distinct neural "signatures" in this temporal lobe region correlate with the vulnerability to stressful experiences. The efficacy of synaptic transmission, as represented by potentiation or suppression of recorded neuronal responses, is an indication of coping adjustments, ie, habituation or behavioral helplessness. Glutamate receptors in this brain region, activated by N-methyl-D-aspartate, are implicated in these behavioral strategies. It is proposed that the neurophysiology of these limbic system structures produces individual differences in stress ulcer severity.

Amygdala↗

PubMed1991

Neural correlates of conditioned odor avoidance in infant rats.

Newborn rat pups can learn to either approach or avoid odor cues through associative conditioning. The present results demonstrate that preference conditioning and avoidance conditioning both modify olfactory bulb responses (focal 2-deoxyglucose uptake and mitral-tufted cell single unit responses) to the conditioned odor. Despite opposing behavioral responses to the conditioned odor, however, olfactory bulb neural responses did not detectably differ between learned odor cues signaling approach and those signaling avoidance. Control pups exhibited neither the behavioral nor neural changes. Furthermore, both the behavioral and neural changes to these odor cues could be extinguished. These results suggest that the olfactory bulb in neonates may code learned odor importance, but specific information attached to that importance may require processing in other brain regions.

Animals↗

PubMed1991

Olfactory associative conditioning in infant rats with brain stimulation as reward: II. Norepinephrine mediates a specific component of the bulb response to reward.

One of the circuits modified by early olfactory learning is in the olfactory bulb. Specifically, response patterns of mitral-tufted cells are modified by associative conditioning during the early postnatal period. In addition, previous work has demonstrated that mitral-tufted cell single units respond to both olfactory conditioned stimuli and rewarding stimulation of the medial forebrain bundle-lateral hypothalamus (MFB-LH). The present study suggests that norepinephrine beta-receptor activation is required for early olfactory learning using MFB-LH stimulation as reward. Propranolol injected before odor-MFB-LH pairings blocks the acquisition of conditioned behavioral responses and their neural correlates to the conditioned odor. Furthermore, propranolol blocks a specific class of the mitral-tufted cell responses to MFB-LH reward stimulation. The relationship of this response to reward and early learning is discussed.

Aging↗

PubMed1991

Olfactory classical conditioning in neonates.

One-day-old, awake infants underwent an olfactory classical conditioning procedure to assess associative learning within the olfactory system of newborns. Experimental infants received ten 30-second pairings of a novel olfactory conditioned stimulus (a citrus odor of neutral value) and tactile stimulation provided by stroking as the reinforcing unconditioned stimulus (a stimulus with positive properties). Control babies received only the odor, only the stroking, or the stroking followed by the odor presentation. The next day, all infants, in either the awake or sleep state, were given five 30-second presentations of the odor. Results were analyzed from video tapes scored by an observer unaware of the infants' training condition. The results indicate that only those infants who received the forward pairings of the odor and stroking exhibited conditioned responding (head turning toward the odor) to the citrus odor. The performance of the conditioned response was not affected by the state of the baby during testing, because both awake and sleeping infants exhibited conditioned responses. Furthermore, the expression of the conditioned response was odor specific; a novel floral odor presented during testing did not elicit conditioned responses in the experimental babies. These results suggest that complex associative olfactory learning is seen in newborns within the first 48 hours of life. These baseline findings may serve as normative data against which observation from neonates at risk for neurological sequelae may be compared.

Conditioning, Classical↗

PubMed1990

Olfactory associative conditioning in infant rats with brain stimulation as reward. I. Neurobehavioral consequences.

In Experiment 1, infant rats were implanted with a stimulating electrode in the medial forebrain bundle/lateral hypothalamus (MFB/LH) on postnatal day 12 (PN12). Four to 6 hours later, the pups underwent associative olfactory conditioning, with half of the pups trained with 30 temporal pairings of odor (5 s) and MFB/LH stimulation (200 Hz, 300 ms), and the other half trained with random presentations of odor and MFB/LH stimulation. On PN13, pups were tested for: (1) behavioral preference for the conditioned odor; (2) focal glomerular layer 2-DG uptake to the odor; or (3) mitral/tufted cell single-unit response pattern to the odor. Odor-MFB/LH pairings produced a relative behavioral preference, enhanced focal 2-DG uptake and a modified mitral/tufted cell response pattern to the conditioned odor. Random training resulted in none of these changes. In Experiment 2, PN12 pups were anesthetized with urethane and single-unit responses of mitral/tufted cells to MFB/LH stimulation were examined. MFB/LH stimulation produced a brief suppression of mitral/tufted cell activity followed either by a prolonged excitation (18/30 cells; 8-10 s duration) or a prolonged suppression (12/30 cells; 10-30 s). These results suggest that pairing olfactory nerve input with MFB/LH stimulation modifies subsequent behavioral and physiological responses to olfactory nerve input alone. Furthermore, the prolonged olfactory bulb response to MFB/LH stimulation may be critical in this modification.

Animals↗

PubMed1990

Modified behavioral and olfactory bulb responses to maternal odors in preweanling rats.

Rat pups acquire an attraction for maternal odors, which can vary with maternal diet. In the two experiments reported here, maternal diet was modified and both pup behavioral responses and pup olfactory bulb neural responses [( 14C]2-DG uptake) to maternal odors were examined. In experiment 1, pups were reared from birth to postnatal day 19 with either a dam fed normal rat chow or a dam fed a sucrose-based diet which suppressed her normal maternal odor. In experiment 2, pups were raised from birth to postnatal day 19 with either a dam fed the sucrose-based diet adulterated with peppermint, or the non-scented sucrose-based diet. Pups selectively expressed both a behavioral attraction and an enhanced olfactory bulb neural response to odors that they experienced in the nest.

Action Potentials↗

PubMed1990

Noradrenergic mechanisms in the central amygdalar nucleus and gastric stress ulcer formation in rats.

Microinjections of noradrenaline (NA, 0.3, 3.0 and 30.0 micrograms) into the central amygdalar nucleus (CEA) produced dose-related attenuations of cold restraint (3 h at 4 degrees C) induced gastric ulcer formation in rats. On the other hand, stress ulcer aggravating effects were seen with beta-adrenoceptor antagonist, propranolol (10 micrograms) but not with the alpha-adrenoceptor antagonist, prazosin (1 and 10 micrograms). Moderate enhancements of gastric stress lesions were also seen with the NA release inhibitor clonidine (1 microgram) and the neurotoxin DSP-4 (25 micrograms). Further, pretreatment of rats with intra-amygdalar (i.am.) propranolol but not prazosin, antagonized and reversed the gastric cytoprotective effects of NA. The results indicate that beta-adrenoceptor-mediated NAergic mechanisms at the level of the CEA are important for the maintenance of gastric mucosal integrity during immobilization stress.

Adrenergic Fibers↗

PubMed1990

Effects of intra-amygdalar thyrotropin releasing hormone (TRH) and its antagonism by atropine and benzodiazepines during stress ulcer formation in rats.

Bilateral intra-amygdalar (i/am) microinjections of TRH (1 and 10 micrograms) and physostigmine (10 micrograms) into the central nucleus (CEA) aggravated cold restraint stress (3 hr at 4 degrees C) induced gastric ulcer formation in rats, whereas atropine (1, 5 and 10 micrograms) attenuated this phenomenon. Similar stress ulcer reducing effects were seen with chlordiazepoxide (CDP, 10 mg/kg, IP) and midazolam (1, 3 and 10 micrograms, i/am). Pretreatment of rats with atropine or CDP antagonized the ulcerogenic effects of both TRH and physostigmine. Further, when administered intra-CEA, midazolam neutralized the effects of TRH in a dose-related manner. These results are discussed in light of TRH-acetylcholine-benzodiazepine/GABA interactions within the amygdaloid complex during stress ulcer formation.

Amygdala↗

PubMed1989

The GABA/benzodiazepine receptor complex in the central amygdalar nucleus and stress ulcers in rats.

The effects of bilateral microinjections of chlordiazepoxide and GABA into the central amygdalar nucleus on gastric ulcer formation induced by cold-restraint were examined in chronically implanted Wistar rats. Higher doses of chlordiazepoxide (20 and 30 micrograms/amygdala) significantly reduced stress ulcer development, whereas a lower dose (2.5 micrograms) produced a nonsignificant increase in ulcer severity. A similar dose/response pattern was observed following GABA administration. The benzodiazepine receptor antagonist Ro15-1788, applied to the amygdala, abolished the protective effects of both chlordiazepoxide and GABA. In addition, when Ro15-1788 (10 micrograms) was injected into the amygdala by itself, it aggravated the gastric stress pathology. However, a lower dose (5 micrograms) had an attenuating effect, opposite to the pattern of effects produced by chlordiazepoxide and GABA. The role of the amygdalar GABA-benzodiazepine receptor complex in stressful conditions is discussed.

Amygdala↗

PubMed1989

Norepinephrine and learning-induced plasticity in infant rat olfactory system.

Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE beta-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE beta-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucose (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-Isoproterenol-Propranolol, or (3) Odor only-Isoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. Thus, NE is sufficient and may be necessary for the acquisition of both learned olfactory behavior and olfactory bulb responses.

Animals↗

PubMed1988

Interactions of thyrotropin-releasing hormone (TRH) with neurotensin and dopamine in the central nucleus of the amygdala during stress ulcer formation in rats.

Bilateral microinjections of thyrotropin-releasing hormone (TRH; 1, 3 and 10 micrograms) into the central nucleus of the amygdala produced a dose-related aggravation of cold restraint-induced gastric ulcers in rats. TRH (10 micrograms) also induced gastric erosions in non-stressed animals. Pretreatment with atropine methyl nitrate attenuated the TRH-induced ulcers in both stress and non-stress situations. TRH (10 micrograms) also antagonized the gastric cytoprotection of intra-amygdalar neurotensin (10 micrograms) and was ineffective in altering the stress ulcer-attenuating effects of dopamine (10 micrograms). Pretreatment with i.p. clozapine, however, prevented the inhibitory effects of dopamine on the TRH-induced aggravation of the gastric stress pathology. The results suggest an interaction of TRH, neurotensin and dopamine in the central amygdalar nucleus during stress, and indicate peripheral cholinergic pathways in the mediation of the ulcerogenic effects of TRH.

Amygdala↗

PubMed1988

Opiate mechanisms in the central amygdala and gastric stress pathology in rats.

Bilateral microinjections of the opiate antagonist naloxone (0.1, 1.0 and 10.0 micrograms) into the central nucleus of the amygdala (CEA) produced a significant potentiation of cold restraint-induced gastric pathology in rats. The opiate agonist, beta-endorphin (0.1, 1.0 and 10.0 micrograms), on the other hand, inhibited stress ulcer formation in a dose-related manner. Stress ulcer-attenuating effects were also seen with intra-CEA injections of the enkephalin analogs [D-Ala2,D-Leu5]enkephalin (10.0 micrograms) and [D-Ala2]Met-enkephalinamide (10.0 micrograms). Pretreatment of rats with naloxone (1.0 microgram) completely antagonized and even reversed the gastric cytoprotective effects of beta-endorphin (1.0 and 10.0 micrograms). The results indicate that the CEA is important in the gastric cytomodulatory effects of endogenous opiates during stressful experiences.

Amygdala↗

PubMed1988

Effects of intra-amygdalar dopamine agonists and antagonists on gastric stress lesions in rats.

Microinjections of dopamine (DA, 3 and 30 micrograms) or its agonist apomorphine (3 micrograms) into the central amygdala (CEA) attenuated cold restraint (3 h at 4 degrees C)-induced gastric ulcer formation in rats. Pretreatment with DA antagonists, haloperidol and metoclopramide (both i.p. and intra-amygdalar) reversed the stress ulcer attenuating effect of DA. It is suggested that the CEA is one of the central sites for this DA cytoprotection and that D2 receptors are possibly involved in this effect.

Amygdala↗

PubMed1988

Reinforcers in infancy: classical conditioning using stroking or intra-oral infusions of milk as UCS.

Six-day-old rats received 20 forward pairings of an odor-conditioned stimulus (CS) with one of two unconditioned stimuli (UCS); 1) intra-oral milk infusions or 2) stroking with a sable-hair brush. These UCS's produce a common general response of increased behavioral activity, but different specific behaviors. For each UCS, additional pups received backward pairings of the CS and UCS, random pairings of the CS and UCS, CS only, UCS only, or no stimuli. Four hours later, pups received a two-odor choice test to assess the development of an odor preference and a CS-only test to assess the acquisition of conditioned responding (CR). The results of the two-odor choice test indicated that for both UCS's only forward pairings of the CS and UCS resulted in an odor preference. Similarly, the CS-only test showed that only forward pairings of the CS and either UCS were effective in producing CR's; pups that received forward pairings exhibited increased behavioral activity during presentations of the CS, which is an unconditioned response (UCR) to both UCS's. Only the forward paired CS-milk UCS group exhibited increased mouthing and probing during the CS only test; these are UCR's that occur to milk infusions but infrequently to the stroking UCS. These results demonstrate the development of similar conditioned odor preferences using behaviorally activating UCS's, but CR's which are specific to the form of the UCR.

Animals↗

PubMed1988

Physical stimulation reduces the body temperature of infant rats.

Physical stimulation of rat pups, of the type normally received from the mother, has been shown to regulate several behavioral and physiological systems in the young. The present paper describes a possible role of physical stimulation in an additional physiological system; the thermoregulatory system. Within a thermoneutral environment, physical stimulation produces a decrease in rectal temperature (Expt. 1). Even in an environment of increasing temperature, similar to that pups experience when in contact with the dam, physical stimulation attenuates an increase in rectal temperature (Expt. 2). The physiological mechanism of heat loss appears to involve ventilatory heat exchange resulting in convective and evaporative heat loss (Expts. 3, 4). Furthermore, physical stimulation continues to produce a decrease in rectal temperature throughout the preweanling period (Expt. 5). These results suggest that pups may not always have to resort to behavioral thermoregulatory mechanisms which require them to separate themselves from their mother. Rather, pups may be cooled, or at least a heat gain attenuated, by physical stimulation from the dam while maintaining contact with her.

Animals↗