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Robert Adamec

Publications and source records attributed to Robert Adamec.

12 recordsLinked to original sources
PubMed2006

Elevated pCREB in the PAG after exposure to the elevated plus maze in rats previously exposed to a cat.

The elevated plus maze (EPM) is an ethologically based test of anxiety-like behavior. In addition, exposure to the maze itself is stressful and anxiogenic. One of the goals of this study was to examine if the stress of EPM exposure increased pCREB-like-immunoreactivity (lir). The second goal of this study was to determine if prior stress impacted expression of pCREB-lir in animals exposed to the EPM. Toward this end, pCREB-lir was examined after exposure to the EPM in young adult male rats that had been exposed to a cat 7 days earlier. Brain areas investigated included the amygdala, periaqueductal gray (PAG), and bed nucleus of the stria terminalis (BNST), all areas considered to be part of the "fear circuit". Results show that there were no pCREB-lir differences between control rats and rats exposed to the EPM only. However, exposure to the EPM in predator stressed rats showed elevated pCREB-lir in the right lateral column of the PAG and bilaterally in the dorsal column of the PAG. In contrast, EPM exposure did not elevate pCREB-lir in the amygdala or BNST in predator stressed rats. Findings suggest mechanisms associated with neuroplasticity may be engaged by relatively mild stresses in animals with a history of severe stress exposure. This may be clinically relevant, as a key feature of posttraumatic stress disorder (PTSD) is the exaggerated reaction to a mild stressor in which the response is more appropriate to the original traumatic situation than the current conditions. If what happens in animals also occurs in humans, the findings of this study suggest that neural mechanisms of prior traumatic stress may interact with subsequent stress to reinforce psychopathology.

Amygdala↗
PubMed2006

Lasting anxiogenic effects of feline predator stress in mice: sex differences in vulnerability to stress and predicting severity of anxiogenic response from the stress experience.

Previous work in male Swiss Webster (CFW) mice demonstrated a long lasting effect of predator stress on risk assessment in the elevated plus maze (EPM). Most severe effects (increases in risk assessment) were seen following a brief unprotected exposure to a cat. Lesser effects were produced by a brief exposure of mice to the cat exposure room without a cat in the room (room stress). This graded response is analogous to the covariation of symptom severity and severity of the precipitating stressor in posttraumatic stress disorder (PTSD). The present study extended these findings to another strain of mice, C57/BL6, and a broader range of tests of anxiety-like behavior, including EPM, acoustic startle response and light/dark box test. Sex was introduced as a variable to investigate if females might be more susceptible to the effects of stressors than males, as has been suggested in human PTSD. Graded and lasting (7 days) effects of a 10 min exposure to a cat (predator stress) or to the cat exposure room only (room stress) were observed on lighted chamber avoidance in the light/dark box. Room stress was without effect on startle responses, but predator stress enhanced peak startle amplitudes measured in the light or in the dark. There was no evidence of light-enhancement of startle in C57 mice. Female mice were more susceptible to the effects of predator and room stress, depending on the measure. Females only responded to cat exposure with a lasting increase in average startle amplitude. This was due to an increased and more prolonged multipeak response to startle after the first and maximal peak startle response. In addition, in females, room and predator stress were equally anxiogenic in measures of open arm avoidance in the EPM. In contrast, room stress was without effect on open arm avoidance in males, but cat exposure was as anxiogenic in males as it was in females. These findings suggest EPM anxiety in females is affected more by the milder stress of room exposure. Severity of effects of predator stress on anxiety-like behaviors in EPM and startle were well predicted (60% of the variance) by measures of cat behavior and probability of mouse defensive response to particular cat behaviors during the cat exposure. Finally, factor analysis indicated that different tests of anxiety-like behavior may be measuring different and independent aspects of mouse affect. Moreover, stressors had no lasting effects on sugar solution consumption. Implications of these findings for modeling PTSD and using transgenic strains of mice to study lasting effects of stress on affect are discussed.

Analysis of Variance↗
PubMed2006

Vulnerability to mild predator stress in serotonin transporter knockout mice.

Effect of predator stress on rat and mouse anxiety-like behavior may model aspects of post traumatic stress disorder (PTSD). A single cat exposure of wild type (C57, CFW) mice can produce lasting anxiety-like effects in the elevated plus maze, light/dark box tests and startle. In addition, female but not male C57 mice are made more anxious in the plus maze by exposure to predator odors alone, suggesting differential vulnerability to predator stressors of differing intensity. There is a link between genetic variation in the serotonin (5-HT) transporter (SERT) and anxiety in humans. This prompted the generation of SERT knockout mice [see Holmes A, Murphy DL, Crawley, JN. Biol Psychiatry 2003;54(10):953-9]. Present work used these mice to determine if there was a link between vulnerability to the anxiogenic effects of predator odors and abnormalities of 5-HT transmission induced by a life long reduction in 5-HT reuptake. Wild type (WT, C57 background), heterozygous (SERT +/-, HET) mice and homozygous knockout (SERT -/-, KO) were assigned to handled control groups or groups exposed for 10 min to a large testing room rich in cat odor. One week after handling or room exposure, anxiety testing took place in the dark phase of the light/dark cycle, in red light. Predator odor exposure was selectively anxiogenic in the plus maze and light/dark box tests in SERT -/- mice. Exposure to predator odor did not potentiate startle. Findings suggest a role for abnormalities in 5-HT transmission in vulnerability to some of the lasting anxiogenic effects of species relevant stressors and possibly in vulnerability to PTSD.

Animals↗
PubMed2005

Protein synthesis and the mechanisms of lasting change in anxiety induced by severe stress.

Brief, unprotected exposure of rats to cats (predator stress) may be lastingly anxiogenic in a variety of tests of rodent anxiety. Recent findings suggest that predator stress induced plasticity in neural circuitry implicated in fear learning underlies some of these anxiogenic effects. In addition, recent work implicates a consolidation-like process in the impact of predator stress on anxiety in that effects of predator stress may be interrupted by immediate post stressor pharmacological interventions. The present study tested whether "consolidation" of the anxiogenic effects of predator stress were dependent on protein synthesis. In addition, the study examined whether a protein synthesis dependent reconsolidation-like process was at work when rats were exposed to a cat twice. Anisomycin (210 mg/kg) or vehicle (Tween 80 in saline) was injected subcutaneously 1 min after a single cat exposure (consolidation test paradigm) or a 1 min after a second cat exposure (reconsolidation test paradigm) and behavior tested 7-8 days after predator stress. In the consolidation test paradigm, anisomycin blocked the anxiogenic effects of predator stress in the elevated plus maze (EPM) measured with open arm exploration. Moreover, anisomycin blocked the potentiation of startle by predator stress when rats were startled in the light, but not when startled in the dark. In contrast, the delay of habituation of startle produced by predator stress was unaffected by anisomycin. Suppression of risk assessment in the EPM by predator stress was not affected by anisomycin either. In startle testing, vehicle injection 1 min after predator stress led to a lasting suppression, rather than enhancement of startle response. Vehicle plus predator stress enhanced and prolonged corticosterone level changes sampled over 30-180 min after treatment when compared to handled or predator stressed only rats. In addition, predator stress plus vehicle suppression of startle was blocked by a benzodiazepine anxiolytic (chloradiazepoxide) or the glucorticoid receptor (GR) blocker RU486. Both drugs returned startle to the predator stressed only heightened levels. It is argued that an added anxiogenic effect of vehicle injection plus predator stress leads to a suppression, rather than enhancement of startle. Startle suppression appears to be mediated, in part, by activation of GR by corticosterone which engages a protein synthesis dependent process, since anisomycin blocked the startle suppressive effects of vehicle. Startle suppression also appeared to be independent of the startle enhancing effect of predator stress and in competition with it. Since predator stress may model aspects of hyperarousal associated with post traumatic stress disorder (PTSD), implications of these findings for understanding of mechanisms of initiation of the disorder and for treatment are discussed.

Analysis of Variance↗
PubMed2005

Role of NMDA receptors in the lateralized potentiation of amygdala afferent and efferent neural transmission produced by predator stress.

The present study investigated the role of NMDA receptors in behavioral and neuroplastic changes in amygdala efferent (central amygdala to periaqueductal gray-ACE-PAG) and amygdala afferent (ventral angular bundle to basolateral amygdala-VAB-BLA) pathways in response to predator stress. Effects on brain and behavioral response to predator stress of competitive block of NMDA receptors with a dose of 10 mg/kg of CPP (3-(2-carboxypiperazin4-yl)propyl-l-phosphonic acid) were studied. Behavioral response to stress was tested with hole board, elevated plus maze, light/dark box, social interaction and acoustic startle tests. CPP was administered i.p. 30 min prior to predator stress and blocked the effects of predator on some but not all behaviors measured 8-9 days later. Effects of predator stress and CPP on potentials evoked in the PAG by single pulse stimulation of the ACE and in the BLA by single pulse stimulation of VAB were assessed 10-11 days after predator stress. Predator stress potentiated ACE-PAG evoked potentials in the right but not the left hemisphere, replicating previous work. Predator stress potentiated VAB-BLA transmission in both hemispheres 10-11 days after predator stress. Right hemisphere VAB-BLA potentiation replicated and extended past studies showing right hemisphere potentiation at 1 and 9 days after stress. Left VAB-BLA potentiation effects differed from the long term depression seen in VAB-BLA at 1 and 9 days after stress in previous studies. CPP blocked predator stress-induced potentiation of ACE-PAG and VAB-BLA evoked potentials in the right hemisphere. CPP did not block left VAB-BLA potentiation, rather CPP amplified it. Left hemisphere effects of CPP were interpreted as reflecting block of NMDA dependent long term depression, which unmasked a non-NMDA dependent potentiation. Taken together, the findings add to a body of evidence suggesting that a syndrome of behavioral changes follows predator stress. Components of this syndrome likely depend on changes in separable neural substrates. Potentiation of ACE-PAG and VAB-BLA evoked potentials in the right hemisphere likely mediates a subset of changes in behavior. Moreover, a medial ACE-PAG pathway is implicated in mediating stress-induced changes in startle amplitude. In contrast, a lateral ACE-PAG pathway is implicated in mediating changes in startle habituation. Finally, consistent with cat and human studies, the right hemisphere appears particularly important in long term response to stress.

Amygdala↗
PubMed2005

Role of NMDA receptors in the syndrome of behavioral changes produced by predator stress.

Effects on behavioral response to predator stress of competitive block of NMDA receptors with doses of .1, 1.0 and 10 mg/kg of CPP (3-(2-carboxypiperazin4-yl)propyl-l-phosphonic acid) were studied. An affect test battery assessed behavioral response to stress and employed hole board, elevated plus maze, light/dark box, social interaction, social avoidance and response to acoustic startle tests. Doses of 1-10 mg/kg of CPP administered ip 30 min prior to predator stress blocked the effects of predator stress on some but not all behaviors measured 8-9 days later. Predator stress normally reduces open arm exploration and risk assessment in the plus maze, decreases entries into the lighted arm of the light dark box and delays habituation of the acoustic startle response. CPP blocked all of these effects of predator stress. A dose of 10 mg/kg of CPP was required for all behaviors except habituation to startle. Block of effects on habituation to startle occurred at 1 and 10 mg/kg. Behaviors in which effects of predator stress were not blocked by CPP included reduction in unprotected head dips in the elevated plus maze and reduced social interaction. In addition, predator stress was without effect on social avoidance measured with the Haller test. These findings extend previous work showing NMDA receptor dependence of effects of predator stress on behavior in the elevated plus maze and on amplitude of acoustic startle response. Novel findings include NMDA receptor dependence of predator stress effects on light dark box behavior and startle habituation. Taken together, the findings add to a body of evidence showing that a syndrome of behavioral changes follows predator stress. Components of this syndrome of behavioral changes likely depend on changes in separable neural substrates initiated in part by NMDA receptors as well as by other neurochemical means.

Analysis of Variance↗
PubMed2005

Anxiolytic and anxiogenic effects of kindling--role of baseline anxiety and anatomical location of the kindling electrode in response to kindling of the right and left basolateral amygdala.

Effects of kindling of right and left basolateral amygdala (BLA) on plus maze anxiety was studied. Using a validated retest paradigm, it was possible to retest rats in the plus maze without increasing anxiety on retest. This permitted determining prekindling baseline levels of plus maze anxiety. Right BLA kindling of high baseline anxiety rats was anxiolytic one week after kindling. Right BLA kindling of low baseline anxiety rats was anxiogenic. In addition, left BLA kindling was either anxiogenic or without effect on plus maze anxiety, depending on baseline anxiety. Effects in left BLA differ from previous work showing anxiolytic effects of left BLA kindling. The discrepancy could be explained in part by prekindling baseline anxiety. These findings require modification of the previous conclusion that left hemisphere (left BLA) kindling is anxiolytic and right BLA kindling is anxiogenic in the plus maze. Rather the hemisphere difference may be due to an interaction between baseline anxiety level and kindling. If true, anxious disposition in rodents may interact with amygdala kindling to change amygdala function differently. Kindling and baseline anxiety effects on other behaviors (such as risk assessment and resistance to capture) are also described. Present data in the light of past studies suggest both premorbid anxiety state and location of the kindling electrode contribute to the effects of kindling on behavior.

Amygdala↗
PubMed2004

Long-lasting, selective, anxiogenic effects of feline predator stress in mice.

Lasting increases in anxiety-like behavior (ALB) are produced by brief exposure of rats to a cat [Adamec RE, Shallow T, Lasting effects on rodent anxiety of a single exposure to a cat, Physiol. Behav., 54 (1993) 101-109.]. Mice also respond defensively to natural predator stimuli. Moreover, chronic exposure of mice to rat odor has immediate anxiogenic effects in plus maze and lasting (7 days) and effects on acoustic startle. The present study examined the lasting (7 days) after effects on ALB of a brief unprotected exposure of male CFW mice to a cat. Lasting effects on ALB of exposure to the cat exposure room were also assessed. Effects on behavior were studied in the hole board and elevated plus-maze (EPM). An ethological analysis of behavior revealed that risk assessment in the EPM was increased the most in predator-stressed mice. Mice exposed to the cat exposure room showed increased risk assessment falling between controls and cat exposed mice. Behavior in the hole board was unaffected, as were most other behaviors in the plus maze. Factor analysis revealed independence of risk assessment from other measures of ALB, activity and exploration, consistent with findings in rats. Aspects of the stress experience were highly predictive of later response to the cat. Cat biting and pawing, mouse fleeing and mouse weight measured at the time of cat exposure together accounted for 71% of the variance of risk assessment in cat exposed mice. The significance of these findings for vulnerability to cat predator stress of mice and for the use of predator stress in mice as a model of aspects of posttraumatic stress disorder (PTSD) are discussed.

Animals↗
PubMed2004

Effects of systemic injections of vilazodone, a selective serotonin reuptake inhibitor and serotonin 1A receptor agonist, on anxiety induced by predator stress in rats.

We examined the effect of Vilazodone, a selective serotonin reuptake inhibitor (SSRI) and serotonin 1A (5-HT(1A)) receptor agonist [Bartoszyk, G.D., Hegenbart, R., Ziegler, H., 1997. EMD 68843, a serotonin reuptake inhibitor with selective presynaptic 5-HT1A receptor agonistic properties. Eur. J. Pharmacol. 322, 147-153.], on change in affect following predator stress. Vilazodone and vehicle injection (intraperitoneal) occurred either 10 min after predator stress (prophylactic testing), or 90 min prior to behavioral testing for the effects of predator stress (therapeutic testing). Predator stress involved unprotected exposure of rats to a domestic cat. Behavioral effects of stress were evaluated with hole board, plus-maze, and acoustic startle tests 1 week after stress. Predator stress increased anxiety-like behavior in the plus-maze and elevated response to acoustic startle. In prophylactic testing, Vilazodone affected stress potentiation of startle at doses above 5 mg/kg. Vilazodone increased stress elevation of startle at 10 mg/kg. Higher doses of Vilazodone (20 and 40 mg/kg) blocked stress potentiation of startle. In contrast, Vilazodone had no effect on stress potentiation of anxiety in the plus-maze. In therapeutic testing, Vilazodone increased stress elevation of startle at all doses. In contrast, therapeutic Vilazodone had no effect on stress potentiation of anxiety in the plus-maze. Taken together, the data suggest a prophylactic potential for Vilazodone in the treatment of changes in hypervigilance following severe stress.

Animals↗
PubMed2004

Prophylactic and therapeutic effects of acute systemic injections of EMD 281014, a selective serotonin 2A receptor antagonist on anxiety induced by predator stress in rats.

We examined the effect of the selective serotonin 2A (5-HT(2A)) receptor antagonist 7-[4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl]-1H-indole-3-carbon itrile HCl (EMD 281014) [Bartoszyk, G.D., van Amsterdam, C., Bottcher, H., Seyfried, C.A., 2003. EMD 281014, a new selective serotonin 5-HT2A receptor antagonist. Eur. J. Pharmacol. 473, 229-230.] on change in affect following predator stress. Predator stress involved a 5 min unprotected exposure of rats to a domestic cat. Behavioral effects of stress were evaluated with hole board, plus maze, light/dark box and acoustic startle tests 1 week after stress. Predator stress increased anxiety-like behavior in the plus maze, light/dark box, and elevated response to acoustic startle. EMD 281014 (0.001, 0.01, 0.1, 1 or 10 mg/kg) and vehicle injection (ip) occurred either 10 min after predator stress (prophylactic testing), or 90 min prior to behavioral testing for the effects of predator stress (therapeutic testing 1 week after predator stress). In prophylactic testing, EMD 281014 prevented stress potentiation of startle in a dose dependent manner, though the most effective doses were midrange (0.01 and 0.1 mg/kg). Prophylactic administration of EMD 281014 also prevented stress-induced increase of open arm avoidance in the plus maze in a clear dose dependent manner (from 0.01 mg/kg onward). In therapeutic testing, EMD 281014 had no clear drug dependent effects on stress elevation of startle or on behavior of stressed rats in the elevated plus maze. Finally, EMD 281014 did not block the effects of stress on behavior in the light/dark box when given prophylactically or therapeutically. Findings implicate 5-HT(2A) receptors in initiation of some but not all lasting changes in anxiety-like behavior following predator stress. Potential clinical significance of findings are discussed.

Animals↗
PubMed2004

Anxiolytic effects of kindling role of anatomical location of the kindling electrode in response to kindling of the right basolateral amygdala.

Study of effects of kindling on affect has been complicated by the fact that anxiogenic, anxiolytic or no effects may be observed following kindling of the amygdala. Factors affecting behavioral outcome include strain of rat, hemisphere kindled, amygdala nucleus kindled and location of the kindling electrodes within particular AP planes of a given nucleus. Previous work has suggested that kindling of the right basolateral amygdala (BLA) is predominantly anxiogenic. This conclusion was based on kindling of anterior or posterior parts of the BLA. The present study sought to clarify this conclusion by examining behavioral effects of right BLA kindling in a mid-range of AP planes not yet studied. A variety of measures of rodent anxiety-like behavior were examined, including behavior in the hole board, elevated plus maze, light/dark box, social interaction test and unconditioned acoustic startle. Anhedonic effects of kindling were assessed by a sucrose preference test with controls for fluid consumption and taste sensitivities. All effects were assessed shortly after kindling (1-2 days) and at a longer time interval (7-8 days). Kindling to four stage 5 seizures in the mid-right BLA altered behavior at all time points after kindling in all tests except the hole board and light/dark box tests. The effect of kindling was anxiolytic like in the plus maze, social interaction and startle tests. Kindling in mid-BLA also increased sucrose consumption. Effects on sucrose consumption are consistent with previous studies showing no depressive-like effects of amygdala kindling in rodents. It is hypothesized that the focal nature of the behavioral consequences of amygdala kindling are best understood in the context of the circuitry in which the cells stimulated are imbedded and the impact of kindling on functioning of those circuits.

Amygdala↗