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Biomedical subjects

J F Brennan

Publications and source records attributed to J F Brennan.

At least 37 records · Page 2Linked to original sources
PubMed1988

Phantom auditory sensation in rats: an animal model for tinnitus.

In order to measure tinnitus induced by sodium salicylate injections, 84 pigmented rats, distributed among 14 groups in five experiments, were used in a conditioned suppression paradigm. In Experiment 1, all groups were trained with a conditioned stimulus (CS) consisting of the offset of a continuous background noise. One group began salicylate injections before Pavlovian training, a second group started injections after training, and a control group received daily saline injections. Resistance to extinction was profound when injections started before training, but minimal when initiated after training, which suggests that salicylate-induced effects acquired differential conditioned value. In Experiment 2 we mimicked the salicylate treatments by substituting a 7 kHz tone in place of respective injections, resulting in effects equivalent to salicylate-induced behavior. In a third experiment we included a 3 kHz CS, and again replicated the salicylate findings. In Experiment 4 we decreased the motivational level, and the sequential relation between salicylate-induced effects and suppression training was retained. Finally, no salicylate effects emerged when the visual modality was used. These findings support the demonstration of phantom auditory sensations in animals.

Animals↗
PubMed1988

An animal model for tinnitus.

Subjective tinnitus remains obscure, widespread, and without apparent cure. In the absence of a suitable animal model, past investigations took place in humans, resulting in studies that were understandably restricted by the nature of human investigation. Within this context, the development of a valid animal model would be considered a major breakthrough in this field of investigation. Our results showed changes in the spontaneous activity of single neurons in the inferior colliculus, consistent with abnormally increased neuronal activity within the auditory pathways after manipulations known to produce tinnitus in man. A procedure based on a Pavlovian conditioned suppression paradigm was recently developed that allows us to measure tinnitus behaviorally in conscious animals. Accordingly, an animal model of tinnitus is proposed that permits tests of hypotheses relating to tinnitus generation, allowing the accommodation of interventional strategies for the treatment of this widespread auditory disorder.

Animals↗
PubMed1988

Maturational influences on perseveration of avoidance and reversal learning after selected brain damage in rats.

In Experiment I, 18 weanling and 18 adult male rats received bilateral electrolytic lesions of the dorsomedial or ventrolateral prefrontal cortex, or the hippocampus, while 12 additional pups and adults served as nonoperated controls (n = 6/group). Subjects were observed for perseverative responding in acquisition of a stepup avoidance task, followed by reversal training and extinction. Thirty days later, subjects were retrained and tested in the same manner. During initial training, the numbers of trials to criteria, errors, and latencies on the last 5 trials all indicated significant effects from age, primarily, and surgery, secondarily. After 30 days, surgical effects assumed a more dominant role, with hippocampal and ventrolateral damage producing the greatest extent of response perseveration. Experiment II replicated the essential procedural sequence as Experiment I, but included damage from combined lesions. 24 weanlings and 24 adults received bilateral lesions to the dorsomedial prefrontal cortex, the dorsomedial prefrontal cortex plus caudate nucleus, or sham lesions. Subjects from this experiment were trained after 7 days or 60 days recovery (n = 6/group). The acquisition results indicated that all independent variables were significant, but only the age effect attained significance in the extinction data. Both experiments point to the profound influence of age at the time of damage in accounting for recovery of avoidance behavior.

Aging↗
PubMed1986

Generalization of a conditioned inhibitor of response suppression in rats.

Following acquisition of conditioned suppression of barpresses to a visual conditiondd stimulus (CS), rats were subjected to a particular variety of differentiation training procedures. An auditory conditioned inhibitor (CI), which preceded and accompanied the CS on some trials, signaled that inescapable shock will not be given on that trial. When the CI acquired the capacity to attenuate markedly the suppressive effects of the CS presented within the CI + CS compound, the frequency dimension of the CI was varied during generalization tests. Reliable within-subjects gradients of barpress enhancement were obtained when tone test frequencies were presented alone. Frequency gradients obtained from CI variation in compound with the CS were rather flat and reflected some residual suppression of the on-going barpressing.

Animals↗
PubMed1982

The efficacy of response prevention on avoidance behavior in young and adult rats with prefrontal cortical injury.

Five days prior to one-way active avoidance training, 36 rats of 18-20 days of age and 36 rats of 110-130 days received dorsomedial, ventrolateral or sham lesions. During acquisition, the CS consisting of the raising of a guillotine door was followed 5 sec later by footshock US onset unless a response was emitted. After acquisition, subjects of each surgical condition were given 1 of 3 extinction treatments. Twelve pups and 12 adults received 5 response prevention trials, in which a second door blocked responses upon CS onset. The same number of subjects was given a delay prior to extinction, and the remaining subjects began extinction immediately following acquisition. Both lesion conditions interfered with adult acquisition, but produced superior acquisition in the lesioned pups, as measured by trials to criterion and trial speeds. In extinction, response prevention seriously disrupted the sham adults, as did the delay condition to a lesser extent. Resistance to extinction decreased to an equivalent extent after both response prevention and delay in the sham pups. An overall disruption in extinction was found in the adult lesioned groups, although there was some evidence of response prevention and delay equivalency in the medial adults. The lesioned pups showed a dramatic persistence responding. A test of passive avoidance to the previous shock compartment was administered 24 h later. Both response prevention and delay treatments in the adults produced residual fear, which was not found in the pups. Rather, all pups behaved with characteristic response inhibitory deficits. The results were considered in light of the prefrontal mediation of response inhibitory centers during ontogeny.

Age Factors↗
PubMed1979

Differential extinction of 2-way active avoidance in young and adult rats.

Three experiments examined age-related differences in extinction of active avoidance in rats through manipulation of the stimulus context. In Experiment I, 36 weanlings and 36 adults acquired comparable avoidance levels to a tonal conditioned stimulus (CS), and novel stimuli consisting of either the presence of a naive rat or a light were presented during 2 tests in extinction. Results indicated more pronounced disruption of extinction in the pups, compared to adults, with the animate novel stimulus having the greater effect. Eighteen pups of 22 days of age and 18 adults in Experiment II were trained to avoid shock with a CS consisting of simultaneous tone and light onset. During extinction responses did not terminate 1 of the CS elements, but rather produced continuation of either the tone or light for an additional 5 sec. Continuation of the tonal element resulted in greater disruption of extinction trials than the light in the adults, although the pups had faster, but nondifferential, extinction rates. A 3rd experiment presented 36 pups and adults with either 0-, 5-, or 10-sec delays of tonal CS reactivation after extinction responses. Both 5- and 10-sec delays resulted in increased numbers of extinction trials in the adults, but the pups failed to respond differentially to any of the delay intervals. Results of all of the experiments were considered in light of species-specific behaviors in avoidance extinction relative to environmental and associative saliencies between ages.

Age Factors↗
PubMed1979

Prefrontal cortical effects on aversively motivated instrumental conditioning in rats: some ontogenic considerations.

During the last 20 years, an emerging body of data has delineated critical variables controlling the acquisition and retention of aversive experiences across ages. Focusing an the rat as subject organism, the behavioral literature on task- and age-specific findings is reviewed. Response inhibitory deficits in younger subjects are related to augmentation of stimulus control through discrimination training and reinstatement of components of original learning. Somewhat parallel and complementary to studies of behavioral development, advances in the neurophysiology and neuroanatomy of cortical functions have indicated the critical role of the prefrontal cortex in acquisition and retention of aversively motivated instrumental responses. Several studies of prefrontal damage administered at varying ages reveal the importance of neural development in both performance deficits as well as recovery of function. These preliminary experiments are discussed in light of constraints from appropriate cortical influences in consideration of the ontogeny of fear.

Animals↗
PubMed1977

Differential effects of dorsomedial prefrontal lesions on active and passive avoidance in young and adult rats.

In Experiment I, four weanling and four adult rats had dorsomedial prefrontal lesions administered prior to initial 2-way avoidance acquisition, while in Experiment II surgical procedures for eight subjects were interpolated between acquisition and a first generalization test along CS tonal frequency. Results indicated impairment of initial avoidance acquisition following lesions, which recovered after a 30-day interval, permitting generalization testing in extinction. When DM lesions were interpolated between acquisition and testing, the effects on avoidance responding were comparatively minimal, but after 30 days lesioned subjects could not reacquire criterion avoidance levels. In all generalization tests there was little evidence of frequency control in lesioned subjects compared to eight sham operated controls of each age. Age effects in both experiments were confined to somewhat greater deficits and less recovery of responding in the pups. Two additional experiments examined passive avoidance acquisition and retention in 144 rats of 18-20, 30-32 and 100+ days of age after dorsomedial prefrontal lesions administered either prior to (Experiment III) or following (Experiment IV) initial training and testing. These data suggested rather minimal lesion effects since variability in retention was readily attributed to age differences. Data were related to prefrontal deficits that are specific to age and task requirements.

Age Factors↗
PubMed1976

Effects of differential cue availability in an active avoidance CS for young and adult rats.

In Experiment I, groups of 22-and 140+-day rats were trained in acquisition and extinction of 1-way avoidance with a CS that consisted of the opening of a guilotine door 5 sec before US onset or a combination of door-opening plus a tonal signal that remained on until the occurrence of the motor response. Under both CS conditions, avoidance acquistion was similar at each age level. The extinction date indicated comparable performance for the young subjects but differential performance and greater resistance to extinction for the adult subjects. Adults trained with the door-opening CS persisted in responding for an entire series of 100 extinction trials, whereas the adults trained with the compound CS extinguished well within the 100-trial, whereas the adults trained with the compound CS extinguished well within the 100-trial limit. A 2nd experiment included 10 pre-exposures of the simple or compound CS's prior to avoidance training. Although the pups were insensitive to pre-exposure effects, the adults that were pre-exposed and trained with identical CS's showed evidence of pre-exposure effects. Results of both experiments were interpreted as indicative of differential cue saliency between ages.

Age Factors↗
PubMed1975

Stimulus generalization of suppression in rats following aversively motivated instrumental or Pavlovian training.

Following 100 or 300 avoidance training trials, instrumental subjects and their yoked Pavlovian counterparts were tested for generalization of lick suppression along the frequency dimension of the avoidance conditioned stimulus. Gradients of stimulus control were evident after 300 instrumental avoidance training trials, and additional intradimensional Pavlovian discrimination training further sharpened the gradients. After 100 trials, the yoked Pavlovian subjects suppressed more than their instrumental counterparts. However, with increased Pavlovian training, flatter gradients with decreased suppression were obtained. Results from a second experiment revealed that, whereas Pavlovian experience decreased suppression to the tone, subjects suppressed drinking in the presence of static, environmental cues. Data from both experiments supported interpretations that stress the role of response control over environmental events.

Acoustic Stimulation↗