Cheryl Kirstein - Academia.edu (original) (raw)

Papers by Cheryl Kirstein

Brain Research, Nov 1, 1991

Young rats learn to approach an odor that has been paired with tactile stimulation. This attracti... more Young rats learn to approach an odor that has been paired with tactile stimulation. This attraction is accompanied by changes in the metabolism and anatomy within the olfactory bulb glomerular layer. In this study, we examined the changes that occur in the olfactory bulb during early olfactory learning, rather than after such pairings have occurred. Specifically, we determined whether the pairing of an odor with tactile stimulation would produce a modified response by olfactory bulb glomerular-layer neurons. To monitor one large subgroup of these neurons during early learning, we used in vivo microdialysis to assess the activity of dopaminergic neurons in the olfactory bulb of postnatal day (PND) 3 rats during simultaneous presentation of odor and tactile stimulation, tactile stimulation alone, odor alone, or clean air alone. Clean air evokes no change in extracellular dopamine (DA), while both odor alone and stroking alone induce prolonged increases in DA peaking at about 200% of baseline. The combination of odor and tactile stimulation, which allows an olfactory preference to be formed, induces a prolonged increase in DA which peaks at about 400% of baseline. The level of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) increases only in pups receiving both odor and tactile stimulation and peaks at about 200% of baseline. With the exception of the pups exposed to clean air, all groups show an increase in homovanillic acid (HVA) of between 150-200% following stimulation. The large and prolonged increase in DA may be linked to the longer term anatomical and physiological changes in the glomerular layer of the bulb that form as a consequence of early olfactory preference training.

bioRxiv (Cold Spring Harbor Laboratory), Jun 25, 2023

doi: bioRxiv preprint BACKGROUND: Serum amyloid A (SAA) proteins increase dramatically in the blo... more doi: bioRxiv preprint BACKGROUND: Serum amyloid A (SAA) proteins increase dramatically in the blood following inflammation. Recently, SAAs are increased in humans following stroke and in ischemic animal models. However, the impact of SAAs on whether this signal is critical in the ischemic brain remains unknown. Therefore, we investigated the role of SAA and SAA signaling in the ischemic brain. METHODS: Wildtype and SAA deficient mice were exposed to middle cerebral artery occlusion and reperfusion, examined for the impact of infarct volumes, behavioral changes, inflammatory markers, TUNEL staining, and BBB changes. The underlying mechanisms were investigated using SAA deficient mice, transgenic mice and viral vectors. RESULTS: SAA levels were significantly increase following MCAo and mice deficient in SAAs showed reduced infarct volumes and improved behavioral outcomes. SAA deficient mice showed a reduction in TUNEL staining, inflammation and decreased glial activation. Mice lacking acute phase SAAs demonstrated a reduction in expression of the NLRP3 inflammasome and SAA/NLRP3 KO mice showed improvement. Restoration of SAA expression via SAA tg mice or adenoviral expression reestablished the detrimental effects of SAA. A reduction in BBB permeability was seen in the SAA KO mice and anti-SAA antibody treatment reduced the effects on ischemic injury.

Psychopharmacology, Feb 1, 1990

Four-day-old (P4) and 21-22-day-old (P21-22) rat pups received an intracisternal injection of eit... more Four-day-old (P4) and 21-22-day-old (P21-22) rat pups received an intracisternal injection of either ACTHI-16NH2 or saline followed by a subcutaneous (SC) injection of saline, the serotonergic (5HT)IA agonists 8-OH-DPAT or ipsapirone, the 5HTzR agonist TFMPP or the 5HTz agonist DOI. The ontogeny of ACTH-induced behaviors including grooming, yawn and stretch as well as various serotonin-related behaviors were recorded via timesampling at 20 s intervals for a test duration of 50 min. ACTH induced slight but significant increases in grooming at P4, along with a significant increase in yawning. At this age the 5HT1B agonist TFMPP induced substantial increases in grooming, with no effect of the other agonists on this behavior. All of the serotonergic agonists, however, decreased ACTH-induced yawning at P4. At P21-22 ACTH induced more robust grooming than that observed at P4, although different in nature from adult-typical ACTH-induced grooming. This ACTH-induced grooming at P21-22 was attenuated by all of the serotonergic agonists, ACTHinduced yawning at P21-22 was not affected by the serotonergic agonists while ACTH-induced stretching was increased by the 5HT~B agonist TFMPP at this age. These data provide additional evidence of differential mediation of various ACTH-induced behaviors, and support other reports of ontogenetic alterations in the response to serotonergic manipulations during the neonatal to weanling age period.

European Journal of Pharmacology, Jun 1, 1990

Preweanling (postnatal day 17-18) Sprague-Dawley rat pups were tested in both the absence and pre... more Preweanling (postnatal day 17-18) Sprague-Dawley rat pups were tested in both the absence and presence of milk following administration of various doses of the 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) or ipsapirone, the 5-HT1B agonist 1-(3-chlorophenyl)piperazine (mCPP) or the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI). 8-OH-DPAT decreased mouthing while ipsapirone, mCPP and DOI had no effect upon this behavior. However, all four agonists significantly decreased grooming. Both 8-OH-DPAT and mCPP produced alterations in limb positioning, with 8-OH-DPAT administration resulting in a poor control of the hindlimbs and mCPP inducing a hindlimb straddle position. These functional responses to 5-HT1A, 5-HT1B and 5-HT2 agonists in preweanling pups vary from those observed previously in neonates. For instance, whereas inhibitory effects of 5-HT1A stimulation on mouthing are observed in both neonatal and preweanling pups, facilitory effects of 5-HT1B and 5-HT2 stimulation are only seen in neonates. These ontogenetic alterations may be related to the previously reported ontogenetic reversal in the effect of serotonergic activation upon mouthing and suckling that occurs during the neonatal to weanling age period.

European Journal of Pharmacology, Jun 1, 1988

Sprague-Dawley rat pups at 3-4 days prenatally were tested in both the absence and presence of mi... more Sprague-Dawley rat pups at 3-4 days prenatally were tested in both the absence and presence of milk following administration of various doses of either the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), the 5-HTIB agonist 1-(3-chlorophenyl)piperazine (mCPP), or the 5-HT 2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2aminopropane (DOI). Administration of 8-OHDP~T decreased mouthing, increased probing and increased behavioral activation. Conversely, the 5-HT 2 agonist DOI and the 5-HTIB agonist mCPP increased mouthing and decreased probing, mCPP and DOI differed in their effects on behavioral activation, with mCPP decreasing and DOI increasing this composite behavioral score, mCPP increased grooming, whereas DOI elicited a characteristic unusual positioning of the limbs. Thus it appears that 5-HTIA, 5-HTln and 5-HT 2 receptor subtypes are present in the neonate and elicit differential behavioral responses upon stimulation with selective agonists. Ontogenetic variations in the balance among these receptor subtypes during development may be related to the ontogenetic reversal that has been previously reported in the impact of serotonin manipulations on mouthing and suckling behavior during the neonatal to weanling age period. 8-OHDPAT (8-hydroxy-2-(di-n-propylamino)tetralin); mCPP (1-(3-chlorophenyl)piperazine); DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane); 5-HT receptor subtypes; Mouthing; (Ontogeny)

Developmental Brain Research, Oct 1, 2005

Adolescence is a time of high risk behavior and increased exploration. This developmental period ... more Adolescence is a time of high risk behavior and increased exploration. This developmental period is marked by a greater probability to initiate drug use and is associated with an increased risk to develop addiction and adulthood dependency. Human adolescents are predisposed toward an increased likelihood of risk taking behaviors [M. Zuckerman, Sensation-seeking and the endogenous deficit theory of drug abuse. NIDA Res Monogr. 74 (1986) 59-70.], including drug use or initiation. In the present study, adolescent and adult animals were first tested on several behavioral measures (novel environment exploratory behavior, novel object preference, novelty-induced impulsivity and noveltyinduced exploration) which were used to categorize them as high-(HR) or low-responders (LR). The purpose of the present study was to characterize the neurochemical responsivity of the nucleus accumbens septi (NAcc) in HR and LR adolescent and adult animals in response to a systemic challenge of cocaine. Regardless of age, animals that were more reactive when placed in a novel environment had greater cocaine-induced increases in dopamine (DA). Several important and complex neurochemical differences existed between adolescent and adult animals. Adolescent animals that rapidly approached the novel object (i.e., HR) were the only group to show greater cocaine-induced responsivity. However, adult animals that spent less time near the novel object (i.e., LR) were the only group to have greater cocaine-induced responsivity. Adolescent animals that approached a novel object faster (HR) showed an increased dopaminergic (DAergic) response to an acute cocaine challenge. In contrast, adolescent animals that spent less time with the novel object had an increased cocaine-induced DAergic response compared to HR adults. Adults that approached the object less had a greater cocaine-induced DA response relative to HR adults. Finally, cocaine yielded a greater DA response in adolescent animals that showed a high novelty-induced exploration and impulsivity response, whereas the opposite was true for adults. The differences in response to cocaine between ages and groups are likely due to ontogenetic differences in brain regions that are involved in reward and/or stress responsivity.

Psychopharmacology, Apr 1, 1989

The distribution of cocaine and the cocaine metabolite benzoylecgonine (BE) in brain and plasma o... more The distribution of cocaine and the cocaine metabolite benzoylecgonine (BE) in brain and plasma of Sprague-Dawley rat dams and their near-term fetuses was assessed 0.5 and 2 h post-injection on gestational day 20 following chronic daily subcutaneous injections of 10, 20, or 40 mg/kg/3 ml cocaine hydrochloride beginning on gestational day 8. Plasma concentrations of cocaine reached in the dams were found to be in the range of, or to exceed, those reported in human cocaine users. Dose-related increases in plasma and brain levels of cocaine in the dams and the fetuses were observed, particularly at 2 h post-injection. Fetal concentrations of cocaine in brain and plasma were approximately 2-3-fold less than those of the dams, suggesting that the placenta may somewhat restrict cocaine entry into fetal circulation. Brain/plasma cocaine ratios, however, were generally equivalent in the dams and fetuses, suggesting that once cocaine enters the circulation, its affinity for brain tissue is similar in the fetus and dam. Whereas plasma levels of BE, like cocaine levels per se, were greater in the dams than fetuses, BE concentrations in fetal brain were greater than those observed in maternal brain. These high levels of BE may contribute to the production of neurobehavioral alterations in cocaine-exposed offspring, given that this active cocaine metabolite has been shown to form molecular complexes with calcium ions (Misra and Mule 1975), thereby having the potential to influence a multiplicity of calcium-regulated developmental events.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Defects Research, 1988

Brain Research, Mar 1, 1991

Olfactory receptor neurons are a CNS entry point for a wide variety of airborne substances. There... more Olfactory receptor neurons are a CNS entry point for a wide variety of airborne substances. Therefore, it is probable that detoxifieation mechanisms are present in these neurons to neutralize such agents. Glutathione (GSH) is an essential component of several detoxification schemes, and in this study we examined the distribution and levels of GSH in the olfactory epithelium, olfactory bulb, cortex, hippocampus and cerebellum in neonatal, weanling, adult and aged rats. We report that GSH is primarily localized to the olfactory receptor neurons and their axons within the olfactory epithelium. It is also localized within the glomernlar neuropil and granule cells of the olfactory bulb. Levels of GSH in the olfactory epithelium and hippocampus do not change as a function of age, although GSH levels decrease in several brain regions, including the olfactory bulb, cerebellum and cortex.

PsycEXTRA Dataset, 1989

Gestational cocaine exposure has an impact on a number of behavioral and physiological measures e... more Gestational cocaine exposure has an impact on a number of behavioral and physiological measures examined during the neonatal to weaning age period. Notable effects of early cocaine exposure include a disruption in cognitive function, along with a profile of DA alterations. Observed physiological differences do not appear to be restricted, however, to the DA system, or even the nervous system. Such data may have important implications regarding the prognosis for future development of human offspring exposed gestationally to cocaine.

Pharmacology, Biochemistry and Behavior, Apr 1, 2007

Developmental Psychobiology, 2005

Adolescence is a time of high-risk behavior and increased exploration. This developmental period ... more Adolescence is a time of high-risk behavior and increased exploration. This developmental period is marked by a greater probability of initiating drug use and is associated with an increased risk to develop addiction and dependency in adulthood. Human adolescents are predisposed towards an increased likelihood of risk taking behaviors (Zuckerman, 1986), including drug use or initiation. The purpose of the study was to examine differences in developmental risk taking behaviors. Adolescent and adult animals were exposed to a novel stimulus in a familiar environment to assess impulsive behaviors, novelty preference, and exploratory behaviors. Adolescent animals had greater noveltyinduced locomotor activity, greater novelty preference, and showed higher approach and exploratory behaviors compared to adult animals. These data support the notion that adolescents may be predisposed toward sensation seeking and consequently, are more likely to engage in risk-taking behaviors, such as drug use initiation.

Adolescence is a period when the brain is undergoing many complex changes that can exert long-ter... more Adolescence is a period when the brain is undergoing many complex changes that can exert long-term influences on decision making and cognitive processes. It is also a period of experimentation. Adolescents demonstrate a more abrupt progression of illicit drug use and development of substance use disorders than adults, suggesting that this ontogenetic period renders the adolescent more vulnerable to addiction. Development of the central nervous system (CNS) during adolescence may play a key role in the increased likelihood to initiate drug use. Topics discussed in this chapter include theories of addiction (anhedonia hypothesis; abberant learning theory; and incentive-sensitization theory); novelty preference and impulse control; conditioned place preference; mesolimbic dopamine (DA) pathway and reward; cocaine and mesolimbic DA system; mesolimbic DA pathway and behavior during adolescence; and impact of cocaine during adolescence

Developmental Psychobiology, 2000

The mesolimbic dopamine (DA) pathway is critical in reward-mediated behavior. Water, sucrose, and... more The mesolimbic dopamine (DA) pathway is critical in reward-mediated behavior. Water, sucrose, and drugs of abuse all increase DA in the nucleus accumbens septi (NAcc) in adult animals. Recently our laboratory has shown that cocaine and alcohol increase DA efflux in preadolescent animals. The present study used a natural reinforcer (i.e., water) at postnatal day 25 (PND 25) to determine the sensitivity and responsiveness of this pathway. Repeated pairing of a peppermint odor with water resulted in a behavioral odor preference and an odor-elicited increase in accumbal DA. Results show that this developing pathway is functional and responsive to conditioning using a natural reinforcer and that these behavioral and neurochemical responses can be conditioned to a previously novel environmental stimulus.

Annals of the New York Academy of Sciences, 1989

Neurotoxicology and Teratology, 1989

Offspring of Sprague-Dawley dams injected SC with 40 mg/kg/3 cc cocaine HCl daily from gestationa... more Offspring of Sprague-Dawley dams injected SC with 40 mg/kg/3 cc cocaine HCl daily from gestational days 8-20, pair-fed dams injected with the vehicle alone and nontreated control dams were examined behaviorally during the early postnatal period. No significant differences were observed among the treatment conditions in maternal weight gain during pregnancy, duration of pregnancy, or number of live male and female pups/litter. Offspring body weights at birth and weaning, physical maturation and reflex development were not significantly affected by prenatal cocaine exposure. In contrast, neonates exposed prenatally to cocaine were observed to exhibit significant deficits in learning of an odor/milk association that nontreated offspring learned and retained for a 24 hr period. On postnatal day 12, cocaine offspring exhibited an increase in locomotor activity and attenuated wall climbing precipitated by footshock, in the absence of any alteration in sensitivity to footshock. Given that wall climbing has been previously shown to be strongly related to levels of catecholamine activity at this age, these data suggest the possibility that there may be some attenuation in catecholaminergic function in pups exposed gestationally to cocaine. The results of this study provide evidence that prenatal cocaine exposure may have an impact upon behavioral and cognitive function even during the early postnatal period. More work is needed to fully characterize the range of alterations observed and the neural mechanisms underlying these early exposure effects.