Search PubMed⌕ Search

Biomedical subjects

Eric S Murphy

Publications and source records attributed to Eric S Murphy.

11 recordsLinked to original sources

Habituation of the head-shake response induces changes in brain matrix metalloproteinases-3 (MMP-3) and -9.

Habituation is defined as a decrease in responsiveness to a repeatedly presented stimulus. The head-shake response (HSR) demonstrates several fundamental properties of habituation including sensitivity to the frequency and intensity of stimulation, and spontaneous recovery. This response shows behavioral plasticity; however the neural plasticity presumed to underlie this behavioral phenomenon has only recently been investigated. The present study initially compared male and female rats and noted equivalent habituation and spontaneous recovery. A second experiment utilized female rats to test the hypothesis that habituation induces changes in neural plasticity. At inter-session intervals (ISIs) of 5 min, 2, 6, and 24 h following HSR habituation independent groups of rats received a second habituation experience, then tissue samples were immediately collected from hippocampal, prefrontal and piriform cortices, and cerebellum. Western blots indicated significant elevations in the expression of matrix metalloproteinase-3 (MMP-3) in hippocampal, prefrontal and piriform cortices at a delay interval of 2 h, and in the prefrontal cortex at 24 h in habituated rats. Increases in active and pro MMP-9 activity were measured by zymography in the hippocampus of habituated rats over yoked controls. Decreases in active MMP-9 activity were seen in the prefrontal cortex, and in pro MMP-9 in the piriform cortex, of habituated as compared with yoked control rats. No changes in MMP-3 or MMP-9 were observed in the cerebellum, and no changes in MMP-2 were seen in any of the four structures examined. These results suggest that habituation of the HSR produced elevations in MMP-3 expression in three of the four structures presently examined, accompanied by increased MMP-9 activity in the hippocampus and decreases in the prefrontal cortex. However, cues present in the test environment appear to have provoked elevations in MMP-3 and -9 independent of those accompanying habituation.

Analysis of Variance↗

Spontaneous recovery and dishabituation of ethanol-reinforced responding in alcohol-preferring rats.

This study examined whether habituation, a decrease in responsiveness to a repeatedly presented stimulus, occurs to ethanol reinforcers in alcohol-preferring (P) rats. Three fundamental properties of habituation were evaluated: generality, spontaneous recovery, and dishabituation. In each experiment, P rats' lever pressing was reinforced by 10% ethanol on a variable-interval 15-s schedule during 50-min sessions. Experiment 1 evaluated the generality of habituation to repeatedly presented stimuli by using ethanol and water reinforcers. Rates of responding were higher for ethanol than they were for water. Additionally, the within-session patterns of responding differed for each reinforcer, suggesting that the pattern of responding was specific to the exact nature of the repeatedly presented reinforcer. Experiment 2 examined spontaneous recovery, an increase in responsiveness to a habituated stimulus when that stimulus is not presented for a time, by separating experimental sessions by 5 min, 2 hr, or 24 hr. Early-session rates of responding during Session 2 were slower than the corresponding rates during Session 1 when sessions were separated by 5 min or 2 hr. Response rates and within-session patterns of responding during Sessions 1 and 2 were similar when sessions were separated by 24 hr. Experiment 3 tested for dishabituation, a restoration of responsiveness following the presentation of an extraneous stimulus, by presenting a tone or a light 24 min and 55 s into the session. Rates of responding temporarily increased after the tone was presented. The results of these experiments support the idea that habituation contributes to the regulation of ethanol consumption.

Alcohol Drinking↗

Stimulus change dis-habituates operant responding supported by water reinforcers.

The present experiment examined whether habituation contributes to within-session decreases in operant responding for water reinforcers. The experiment asked if this responding can be dis-habituated, a fundamental property of habituated behavior. During baseline, rats' lever pressing was reinforced by water on a variable interval 15-s schedule. During experimental conditions, rats responded on the same schedule and a new stimulus was introduced for 5 min at 15, 30 or 45 min into the 60-min session. The new stimulus was extinction, continuous reinforcement or flashing lights in different conditions. Rate of responding primarily decreased within the session during baseline. Introducing a new stimulus sometimes suppressed (extinction, continuous reinforcement) and sometimes increased (flashing lights) responding while it was in effect. The new stimulus increased responding after it ended and before it was presented in the session. The results are incompatible with the idea that non-habituation satiety factors (e.g., cellular hydration and blood volume) contributed to within-session changes in responding. These satiety factors should increase with increases in consumption, decrease with decreases in consumption and remain constant with constant consumption of water. Nevertheless, all stimulus changes increased operant responding for water. These results support the idea that habituation contributes to within-session decreases in responding for water reinforcers.

Animals↗

Role of mitogen-activated protein kinases during recovery from head-shake response habituation in rats.

Habituation is defined as a decrease in responsiveness to a repeatedly presented stimulus. The head-shake response (HSR) consists of a rapid twisting of the head about the front-to-rear axis elicited by a stream of air to the ear. This response demonstrates several fundamental properties of habituation including sensitivity to the frequency and intensity of stimulation, and spontaneous recovery. Despite an abundance of behavioral data on the HSR, relatively little is known about its physiological mechanism(s). To address this issue, changes in mitogen-activated protein kinases (MAPK) were assessed 5 min and 2, 6, and 24 h following the habituation of the HSR. Three cascades of MAPK activity were measured in the cerebellum and hippocampal, prefrontal, and piriform cortices, including extracellular-response kinase (ERK), p-38 kinase (p-38), and stress-activated protein kinase (SAPK). Significant activation of p-38 and SAPK was observed in all four brain structures, accompanied by modest changes in ERK activity. Recovery of the HSR was characterized by decreasing MAPK activation with control levels re-established 24 h after habituation. The present results suggest that MAPK activation mediates recovery from habituation; however, these findings may also support alternative interpretations such that MAPK activation reflects the encoding of spatial cues associated with the testing environment and/or are due to stress induced by the habituation protocol.

Animals↗

Regulation of drug taking by sensitization and habituation.

The authors argue that drug taking is an operant behavior that is reinforced by the drug itself. The effectiveness of a drug as a reinforcer is modulated by sensitization and habituation to the drug as it is consumed. According to this model, drug taking stops when habituation reduces the ability of the drug to reinforce its own consumption. Drug taking resumes when spontaneous recovery restores the effectiveness of the drug as a reinforcer. This parsimonious model provides a framework for understanding many findings in the drug literature, including acute and chronic tolerance, the effect of deprivation on consumption, the contextual specificity of tolerance, polydrug abuse, cross-sensitization between stress and drugs, behavioral sensitization, priming, and reinstatement. Although this model cannot explain all aspects of drug taking (e.g., the effect of cognitive manipulations), it has many implications for understanding and controlling human drug consumption and addiction.

Animals↗

Influence of hippocampectomy on habituation, exploratory behavior, and spatial memory in rats.

Two frequently cited functions of the hippocampus are mediation of spatial memories and habituation. The present investigation employed head-shake response (HSR) as the habituated behavior in intact and bilaterally hippocampectomized rats. This HSR appears to be minimally influenced by spatial cues. These rats were further tested on two behavioral paradigms that make use of spatial cues, namely open field object exploration, and the Morris water maze. The results indicate that hippocampectomized rats revealed habituation of the HSR, but not to objects within the open field. In agreement with previous reports, hippocampectomized rats were severely impaired both in acquiring and recalling the location of the submerged platform in the Morris water maze task. In a separate experiment independent groups of rats were trained on one of these three paradigms, and tissues were collected from hippocampal, prefrontal, and piriform cortices for the measurement of matrix metalloproteinases (MMPs) as markers of neural plasticity. There were significant MMP-9 elevations in the prefrontal and piriform cortices of rats tested using the object exploration task, in the prefrontal and hippocampal cortices of rats that solved the Morris water maze task, but minimal MMP changes in any tissues taken from HSR habituated rats. These results question the hypothesis that habituation is solely mediated by the hippocampus in favor of a process that utilizes different brain structures and degrees of neural plasticity dependent upon task requirements.

Animals↗

Varying reinforcer duration produces behavioral interactions during multiple schedules.

The experiments tested the idea that changes in habituation to the reinforcer contribute to behavioral interactions during multiple schedules. This idea predicts that changing an aspect of the reinforcer should disrupt habituation and produce an interaction. Pigeons and rats responded on multiple variable interval variable interval schedules. Introducing variability into the duration of reinforcers in one component increased response rates in both components when the schedules provided high, but not low, rates of reinforcement. The increases in constant-component response rates grew larger as the session progressed. Within-session decreases in responding were smaller when the other component provided variable-, rather than fixed-, duration reinforcers. These results are consistent with the idea that changes in habituation to the reinforcer contribute to behavioral interactions. They help to explain why interactions do not occur for some subjects under conditions that produce them for others. Finally, the results question the assumption that induction and behavioral contrast are always produced by different theoretical mechanisms.

Animals↗

Extinguished operant responding shows stimulus specificity.

The experiment tested for stimulus specificity in extinguished operant responding. Eight pigeons pecked keys for food reinforcers delivered by a variable interval (VI) 60-s schedule. The key was illuminated with red light during some sessions and white light during others. Then, responding was placed on extinction. During some sessions of extinction, the color of the key light remained constant throughout the session (red or white). During other sessions the color changed at 30 min into the session (red to white or white to red). Response rate increased after the change of key color in extinction. If it is assumed that key color is part of the stimulus to which subjects habituate, then these results are consistent with McSweeney and Swindell's [J. Gen. Psychol. 129 (2002) 364] suggestion that responding declines in extinction partly because subjects habituate to the stimuli that support conditioned responding. Habituation is relatively specific to the exact nature of the stimulus presented. Therefore, changes in the stimulus violate stimulus specificity and restore habituated responding. The results are also consistent with other theories that attribute extinction to a reduction of stimulus control [e.g., Psychol. Bull. 114 (1993) 80; J. Exp. Psychol.: Anim. Behav. Process. 16 (1990) 235], but considerations such as parsimony and testability favor the habituation hypothesis over these theories.

Animals↗

The relation of multiple-schedule behavioral contrast to deprivation, time in session, and within-session changes in responding.

Pigeons' keypecking was reinforced by food on baseline schedules of multiple variable interval (VI) x VI x and on contrast schedules of multiple VI x VI y. Deprivation of food was varied by maintaining subjects at 75%, 85%, and 95% (+/- 2%) of their free-feeding weights. Positive and negative behavioral contrast were observed. The size of the contrast was not systematically altered by changes in deprivation. Positive and negative contrast were both larger later in the session than they were earlier. Within-session decreases in responding were steeper for the baseline than for the contrast schedules for positive contrast. Within-session decreases were steeper for the contrast than for the baseline schedules for negative contrast. These results were predicted by the idea that different amounts of habituation to the reinforcer during the baseline and contrast schedules contribute to behavioral contrast. The results show that contrast occurs under conditions that reduce the effect of the following component. The results support the assumption that positive and negative contrast are produced by symmetrical theoretical variables.

Animals↗

Dynamic changes in reinforcer effectiveness: theoretical, methodological, and practical implications for applied research.

Reinforcers lose their effectiveness when they are presented repeatedly. Traditionally, this loss of effectiveness has been labeled satiation. However, recent evidence suggests that habituation provides a more accurate and useful description. The characteristics of behavior undergoing satiation differ for different stimuli (e.g., food, water), and these characteristics have not been identified for the noningestive reinforcers often used by applied behavior analysts (e.g., praise, attention). As a result, the term satiation provides little guidance for either maintaining or reducing the effectiveness of reinforcers. In contrast, the characteristics of behavior undergoing habituation are well known and are relatively general across species and stimuli. These characteristics provide specific and novel guidance about how to maintain or reduce the effectiveness of a reinforcer. In addition, habituation may lead to a better understanding of several puzzling phenomena in the conditioning literature (e.g., extinction, behavioral contrast), and it may provide a more precise and accurate description of the dynamics of many different types of behavior.

Animals↗

The effect of rate of reinforcement and time in session on preference for variability.

Pigeons pecked keys on concurrent-chains schedules that provided a variable interval 30-sec schedule in the initial link. One terminal link provided reinforcers in a fixed manner; the other provided reinforcers in a variable manner with the same arithmetic mean as the fixed alternative. In Experiment 1, the terminal links provided fixed and variable interval schedules. In Experiment 2, the terminal links provided reinforcers after a fixed or a variable delay following the response that produced them. In Experiment 3, the terminal links provided reinforcers that were fixed or variable in size. Rate of reinforcement was varied by changing the scheduled interreinforcer interval in the terminal link from 5 to 225 sec. The subjects usually preferred the variable option in Experiments 1 and 2 but differed in preference in Experiment 3. The preference for variability was usually stronger for lower (longer terminal links) than for higher (shorter terminal links) rates of reinforcement. Preference did not change systematically with time in the session. Some aspects of these results are inconsistent with explanations for the preference for variability in terms of scaling factors, scalar expectancy theory, risk-sensitive models of optimal foraging theory, and habituation to the reinforcer. Initial-link response rates also changed within sessions when the schedules provided high, but not low, rates of reinforcement. Within-session changes in responding were similar for the two initial links. These similarities imply that habituation to the reinforcer is represented differently in theories of choice than are other variables related to reinforcement.

Animals↗