Age-related Differences In Sensitivity Research Articles

Revisiting specific force loss in human permeabilised single skeletal muscle fibres obtained from older individuals.

Specific force (SF) has been shown to be reduced in some but not all studies of human ageing using chemically skinned single muscle fibres. This may be due in part to the health status/physical activity levels of different older cohorts, but also from methodological differences in studying skinned fibres. The aim of the present study was to compare SF in fibres from older hip fracture patients (HFP), healthy master cyclists (MC) and healthy non-trained young adults (YA) using two different activating solutions. Quadriceps muscle samples and 316 fibres were obtained from HFPs (74.6±4 years, n=5), MCs (74.8±1, n=5) and YA (25.5±2, n=6). Fibres were activated (pCa 4.5, 15oC) in solutions containing either 60 mM TES or 20 mM imidazole. SF was determined by normalising force to fibre CSA assuming either an elliptical or circular shape and to fibre myosin heavy chain content. Activation in TES resulted in significantly higher MHC-I SF in all groups and YA MHC-IIA fibres, irrespective of normalisation method. Whilst there were no differences in SF between the participant groups, the ratio of SF between the TES and imidazole solutions was lower in HFPs compared to YAs (MHC-I p<0.05; MHC-IIA p=0.055). Activating solution composition, as opposed to donor characteristics, had a more notable effect on single fibre SF. However, this two-solution approach revealed an age-related difference in sensitivity in HFPs which was not shown in MCs. This suggests further novel approaches may be required to probe age/activity-related differences in muscle contractile quality.

Acute Toxicity of 6PPD-Quinone to Early Life Stage Juvenile Chinook (Oncorhynchus tshawytscha) and Coho (Oncorhynchus kisutch) Salmon.

The breakdown product of the rubber tire antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD)-6-PPD-quinone has been strongly implicated in toxic injury and death in coho salmon (Oncorhynchus kisutch) in urban waterways. Whereas recent studies have reported a wide range of sensitivity to 6PPD-quinone in several fish species, little is known about the risks to Chinook salmon (Oncorhynchus tshawytscha), the primary prey of endangered Southern Resident killer whales (Orcinus orca) and the subject of much concern. Chinook face numerous conservation threats in Canada and the United States, with many populations assessed as either endangered or threatened. We evaluated the acute toxicity of 6PPD-quinone to newly feeding (~3 weeks post swim-up) juvenile Chinook and coho. Juvenile Chinook and coho were exposed for 24 h under static conditions to five concentrations of 6PPD-quinone. Juvenile coho were 3 orders of magnitude more sensitive to 6PPD-quinone compared with juvenile Chinook, with 24-h median lethal concentration (LC50) estimates of 41.0 and more than 67 307 ng/L, respectively. The coho LC50 was 2.3-fold lower than what was previously reported for 1+-year-old coho (95 ng/L), highlighting the value of evaluating age-related differences in sensitivity to this toxic tire-related chemical. Both fish species exhibited typical 6PPD-quinone symptomology (gasping, increased ventilation, loss of equilibrium, erratic swimming), with fish that were symptomatic generally exhibiting mortality. The LC50 values derived from our study for coho are below concentrations that have been measured in salmon-bearing waterways, suggesting the potential for population-level consequences in urban waters. The higher relative LC50 values for Chinook compared with coho merits further investigation, including for the potential for population-relevant sublethal effects. Environ Toxicol Chem 2023;42:815-822. © 2023 His Majesty the King in Right of Canada and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Fisheries and Oceans Canada.

Age-related differences in ventral striatal and default mode network function during reciprocated trust

Social relationships change across the lifespan as social networks narrow and motivational priorities shift to the present. Interestingly, aging is also associated with changes in executive function, including decision-making abilities, but it remains unclear how age-related changes in both domains interact to impact financial decisions involving other people. To study this problem, we recruited 50 human participants (Nyounger = 26, ages 18–34; Nolder = 24, ages 63–80) to play an economic trust game as the investor with three partners (friend, stranger, and computer) who played the role of investee. Investors underwent functional magnetic resonance imaging (fMRI) during the trust game while investees were seated outside of the scanner. Building on our previous work with younger adults showing both enhanced striatal responses and altered default-mode network (DMN) connectivity as a function of social closeness during reciprocated trust, we predicted that these relations would exhibit age-related differences. We found that striatal responses to reciprocated trust from friends relative to strangers and computers were blunted in older adults relative to younger adults, thus supporting our primary pre-registered hypothesis regarding social closeness. We also found that older adults exhibited enhanced DMN connectivity with the temporoparietal junction (TPJ) during reciprocated trust from friends compared to computers while younger adults exhibited the opposite pattern. Taken together, these results advance our understanding of age-related differences in sensitivity to social closeness in the context of trusting others.

Ontogeny of Pediatric Pharmacogenetics: Celebrating the Past and Vision for the Future.

Ontogeny of Pediatric Pharmacogenetics: Celebrating the Past and Vision for the Future.

The effects of age on reward magnitude processing in the monetary incentive delay task

Previous studies have suggested age-related differences in reward-directed behavior and cerebral processes in support of the age effects. However, it remains unclear how age may influence the processing of reward magnitude. Here, with 54 volunteers (22–74 years of age) participating in the Monetary Incentive Delay Task (MIDT) with explicit cues ($1, ¢1, or nil) and timed response to win, we characterized brain activations during anticipation and feedback and the effects of age on these regional activations. Behaviorally, age was associated with less reaction time (RT) difference between dollar and cent trials, as a result of slower response to the dollar trials; i.e., age was positively correlated with RT dollar – RT cent, with RT nil as a covariate. Both age and the RT difference ($1 - ¢1) were correlated with diminished activation of the right caudate head, right anterior insula, supplementary motor area (SMA)/pre-SMA, visual cortex, parahippocampal gyrus, right superior/middle frontal gyri, and left primary motor cortex during anticipation of $1 vs. ¢1 reward. Further, these regional activities mediated the age effects on RT differences. In responses to outcomes, age was associated with decreases in regional activations to dollar vs. cent loss but only because of higher age-related responses to cent losses. Together, these findings suggest age-related differences in sensitivity to the magnitude of reward. With lower cerebral responses during anticipation to win large rewards and higher responses to outcomes of small loss, aging incurs a constricted sensitivity to the magnitude of reward.

Differential Effects of Nicotine Exposure on the Hippocampus Across Lifespan.

: BackgroundNicotine exposure affects the hippocampus through activation of hippocampal nicotinic acetylcholine receptors (nAChRs), which are present throughout excitatory and inhibitory hippocampal circuitry. The role of cholinergic functioning in the hippocampus varies across developmental stages so that nicotine exposure differentially affects this region depending upon timing of exposure, producing developmentally distinct changes in structure, function, and behavior.MethodsWe synthesize findings across literature in this area to comprehensively review current understanding of the unique effects of nicotine exposure on the hippocampus throughout the lifespan with a focus on hippocampal morphology, cholinergic functioning, and hippocampus-dependent learning and memory.ConclusionsChronic and acute nicotine exposure differentially affect hippocampus structure, functioning, and related learning and memory in the perinatal period, adolescence, and aging. Age-related differences in sensitivity to nicotine exposure should be considered in the research of nicotine addiction and the development of nicotine addiction treatments.

Pre-adolescent and adolescent mice are less sensitive to the effects of acute nicotine on extinction and spontaneous recovery

Adolescence is a period of high risk for the initiation of nicotine product usage and exposure to traumatic events. In parallel, nicotine exposure has been found to age-dependently modulate acquisition of contextual fear memories; however, it is unknown if adolescent nicotine exposure alters extinction of fear related memories. Age-related differences in sensitivity to the effects of nicotine on fear extinction could increase or decrease susceptibility to anxiety disorders. In this study, we examined the effects of acute nicotine administration on extinction and spontaneous recovery of contextual fear memories in pre-adolescent (PND 23), late adolescent (PND 38), and adult (PND 53) C57B6/J mice. Mice were first trained in a background contextual fear conditioning paradigm and given an intraperitoneal injection of one of four doses of nicotine (0.045, 0.09, 0.18, or 0.36mg/kg, freebase) prior to subsequent extinction or spontaneous recovery sessions. Results indicated that all acute nicotine doses impaired extinction of contextual fear in adult mice. Late adolescent mice exhibited impaired extinction of contextual fear only following higher doses of acute nicotine, and extinction of contextual fear was unaffected by acute nicotine exposure in pre-adolescent mice. Finally, acute nicotine exposure enhanced spontaneous recovery of fear memory, but only in adult mice. Overall, our results suggest that younger mice were less sensitive to nicotine’s impairing effects on extinction of contextual fear and to nicotine’s enhancing effects on spontaneous recovery of contextual fear memory.

Age-related differences in sensitivity to metals can matter for Daphnia magna neonates.

Age-related differences in sensitivity to metals can matter for Daphnia magna neonates.

Cocaine self-administration punished by intravenous histamine in adolescent and adult rats.

Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability.

Poster #M14 USE OF FOLATE TO PREVENT SCHIZOPHRENIA IN ANIMAL MODEL OF KETAMINE INDUCE SCHIZOPHRENIA IN RATS

Acetylcholine (ACh) release is modulated pre-synaptically by both muscarinic and nicotinic receptor-mediated processes. While muscarinic autoreceptors inhibit ACh release, nicotinic autoreceptors enhance ACh release and thus disruption of these processes could potentially affect cholinergic toxicity following exposure to anticholinesterases. Marked age-related differences in sensitivity to some organophosphorus (OP) anticholinesterases have been reported. We compared nicotinic autoreceptor function (NAF) during maturation and aging and evaluated its potential modulation by the common OP insecticide, chlorpyrifos (CPF). Cortical synaptosomes were pre-loaded with [3H]choline, superfused (0.6 ml/min) with physiological buffer and [3H]ACh release was evoked with potassium (KCl, 9 mM), with or without co-addition of exogenous ACh to stimulate nicotinic autoreceptors. Fractions of perfusate were subsequently collected and area under the curve (AUC) for [3H] was analyzed by scintillation counting. The difference in evoked release due to co-addition of exogenous ACh was defined as NAF. Under these conditions, atropine (ATR, 0.1 μM) appeared requisite for NAF; thus this muscarinic antagonist was subsequently added to all perfusion buffers. In synaptosomes from adult tissues, exogenous ACh (3–100 μM) significantly increased release in a concentration-dependent manner. The nicotinic antagonist mecamylamine (MEC, 100 μM) substantially reduced the potassium-evoked release elicited by co-addition of ACh (10 μM). Interestingly, the nicotinic agonists nicotine (NIC) and dimethylphenylpiperazinium (DMPP; 0.1–10 μM) had no effect on release. The active metabolite of CPF (i.e. chlorpyrifos oxon (CPO), 1–10 μM) inhibited NAF in vitro. Maturation-related expression of NAF was noted (AUC with co-addition of 10 μM ACh: 7-day rats, 7±6; 21-day rats, 44±6; 90-day rats, 196±37; 24-month rats, 173±52). NAF was substantially reduced (67–91%) 96 h after maximum tolerated dosages of CPF in adult and aged rats (279 mg/kg, sc) but not in juveniles (127 mg/kg, sc), even though AChE inhibition was similar among the age groups (>80%). Together these data suggest that NAF is differentially expressed during maturation and that this neuromodulatory process may be selectively altered by some OP insecticides, potentially contributing to age-related differences in response to AChE inhibitors. As NAF has been postulated to be activated under conditions of ‘impaired’ cholinergic function, selective alteration of this pre-synaptic process by OP anticholinesterases may be also important in age-related conditions associated with cholinergic hypofunction.

Developmental differences in EEG and sleep responses to acute ethanol administration and its withdrawal (hangover) in adolescent and adult Wistar rats

Age-related differences in sensitivity to the acute effects of alcohol may play an important role in the increased risk for the development of alcoholism seen in teens that begin drinking at an early age. The present study evaluated the acute and protracted (hangover) effects of ethanol in adolescent (P33–P40) and adult (P100–P107) Wistar rats, using the cortical electroencephalogram (EEG). Six minutes of EEG was recorded during waking, 15 min after administration of 0, 1.5, or 3.0 g/kg ethanol, and for 3 h at 20 h post ethanol, during the rats' next sleep cycle. Significantly higher overall frontal and parietal cortical power was seen in a wide range of EEG frequencies in adolescent rats as compared to adult rats in their waking EEG. Acute administration of ethanol did not produce differences between adolescents and adults on behavioral measures of acute intoxication. However, it did produce a significantly less intense acute EEG response to ethanol in the theta frequencies in parietal cortex in the adolescents as compared to the adults. At 20 h following acute ethanol administration, during the rats' next sleep cycle, a decrease in slow-wave frequencies (1–4 Hz) was seen and the adolescent rats were found to display more reduction in the slow-wave frequencies than the adults did. The present study found that adolescent rats, as compared to adults, demonstrate low sensitivity to acute ethanol administration in the theta frequencies and more susceptibility to disruption of slow-wave sleep during hangover. These studies may lend support to the idea that these traits may contribute to increased risk for alcohol use disorders seen in adults who begin drinking in their early teenage years.

Age-related Differences in Processing Face Configuration: The Importance of the Eye Region

Recent research suggests that older adults have difficulties with aspects of configural face processing. The present study examined whether age-related declines in sensitivity to configural face information are dependent on the face region in which configural changes occur. Younger and older adults completed a face-matching task that required the detection of configural manipulations to either the eye or the mouth regions of target faces. Age-related declines in the ability to detect configural changes were found when the eye region of the face was modified. Importantly, no age-related differences were evident when perceiving similar changes to the mouth region. Taken together, these findings suggest that age-related differences in sensitivity to configural information are specific to the eye region of the face. The potential implications of these findings for age-related difficulties in interpreting social cues from the eyes are discussed.

Electrocardiographic diagnosis of left-ventricular hypertrophy

Electrocardiographic diagnosis of left-ventricular hypertrophy

Lingual tactile acuity and food texture preferences among children and their mothers

Despite anecdotal reports of children being more sensitive to texture than adults, and of texture being one of the main drivers of food aversions, there is a paucity of scientific knowledge on the influence of texture perception on food choice in children. The primary goals of this study were to assess the use of a modified letter-identification task to study lingual tactile acuity, one aspect of oral sensitivity, in children and to examine age-related differences in sensitivity. The secondary goal was to explore whether lingual tactile acuity and age relate to various measures of food choice and preference. To this end, children 7–10years old (31 girls, 21 boys) and their mothers were tested using identical procedures. To assess lingual tactile acuity, children and mothers were asked to use the tips of their tongues to identify raised alphabetical letters of varying size (2.5–8.0mm) on Teflon strips. To relate lingual tactile acuity to food texture preferences, a forced-choice questionnaire assessed preferences for foods similar in flavor but different in texture (e.g., smooth versus crunchy peanut butter). Children were able to complete the lingual acuity task as well as their mothers and took less time to assess each letter stimulus (p<0.001); however, there were no age-related differences in lingual acuity (p=0.14). Age, but not lingual acuity, related to food texture preferences: mothers preferred harder foods (p<0.001) and those containing more particles (p<0.04) than did children, although children’s preferences became more adult-like with increasing age. The availability of a rapid, child-friendly method for assessing oral sensitivity opens up new possibilities of examining differences in oral tactile perceptions across the life span. That food preferences changed with age and were not related to oral sensitivity underscores the fact that factors such as family food practices, culture and experience have a significant impact on children’s food texture preferences.

Risk, Reward, and Decision-Making in a Rodent Model of Cognitive Aging

Impaired decision-making in aging can directly impact factors (financial security, health care) that are critical to maintaining quality of life and independence at advanced ages. Naturalistic rodent models mimic human aging in other cognitive domains, and afford the opportunity to parse the effects of age on discrete aspects of decision-making in a manner relatively uncontaminated by experiential factors. Young adult (5–7 months) and aged (23–25 months) male F344 rats were trained on a probability discounting task in which they made discrete-trial choices between a small certain reward (one food pellet) and a large but uncertain reward (two food pellets with varying probabilities of delivery ranging from 100 to 0%). Young rats chose the large reward when it was associated with a high probability of delivery and shifted to the small but certain reward as probability of the large reward decreased. As a group, aged rats performed comparably to young, but there was significantly greater variance among aged rats. One subgroup of aged rats showed strong preference for the small certain reward. This preference was maintained under conditions in which large reward delivery was also certain, suggesting decreased sensitivity to reward magnitude. In contrast, another subgroup of aged rats showed strong preference for the large reward at low probabilities of delivery. Interestingly, this subgroup also showed elevated preference for probabilistic rewards when reward magnitudes were equalized. Previous findings using this same aged study population described strongly attenuated discounting of delayed rewards with age, together suggesting that a subgroup of aged rats may have deficits associated with accounting for reward costs (i.e., delay or probability). These deficits in cost-accounting were dissociable from the age-related differences in sensitivity to reward magnitude, suggesting that aging influences multiple, distinct mechanisms that can impact cost–benefit decision-making.

Ethanol‐Induced Conditioned Taste Aversion in Male Sprague‐Dawley Rats: Impact of Age and Stress

Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment. Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption.

Repeated restraint stress alters sensitivity to the social consequences of ethanol in adolescent and adult rats

Human adolescents consume alcohol largely to enhance social interactions. Adolescent, but not adult rats likewise exhibit ethanol-induced social facilitation under low-stress circumstances. Since the relationship between stress and ethanol sensitivity across ontogeny still has yet to be well explored, the present study sought to characterize possible age-associated differences in the influence of stressor exposure on ethanol-induced changes in social behavior in adolescent [postnatal days (P) 30–36] and adult (P65–71) male and female Sprague–Dawley rats. Animals were repeatedly restrained (90 min/day) for 5 days, followed by examination of ethanol-induced (0, 0.25, 0.5, 0.75, or 1.0 g/kg) alterations in social behaviors on the last day. Results revealed typical age-related differences in sensitivity to ethanol among controls, with adolescents being uniquely sensitive to low-dose ethanol stimulation of social investigation and play fighting, but less sensitive than adults to the social suppression emerging at higher doses. At both ages, stressor exposure decreased sensitivity to social inhibitory effects of ethanol, while augmenting expression of ethanol's social facilitatory effects. Ethanol also attenuated the stress-related suppression of social motivation at both ages. These results suggest that repeated stressor exposure diminishes age-related differences in the social consequences of ethanol, with stress enhancing ethanol-induced social facilitation across age.

Age-related differences in sensitivity to small changes in frequency assessed with cortical evoked potentials

As part of an ongoing study of age-related changes in auditory processing, sensitivity to small changes in frequency were assessed using the cortical auditory evoked potential, P1-N1-P2, in younger and older adults with normal hearing. Behavioral measures have shown age-related differences in intensity and frequency discrimination that are larger at lower than higher frequencies. However, substantial individual differences and equivocal results among studies have been reported. This variability may reflect differences in tasks and procedures, as well as subject variables, such as hearing sensitivity and level of attention. To minimize these subject variables, the P1-N1-P2 response was investigated using a passive listening paradigm. Subjects were 10 younger and 10 older adults. The P1-N1-P2 was elicited by a 150-ms change in frequency in otherwise continuous 500-Hz and 3000-Hz pure tones presented at 70 dB SPL. P1-N1-P2 threshold was defined as the smallest change in frequency needed to evoke a P1-N1-P2 response. Furthermore, a frequency-dependent aging effect was observed for P1-N1-P2 thresholds, such that older subjects were significantly less sensitive to the frequency change than younger subjects, with significantly larger age-related differences at 500 Hz than at 3000 Hz. Age-related changes in response latencies and amplitude of the P1-N1-P2 response were also evident at 500 and 3000 Hz. These results are consistent with age-related changes in the central auditory system and suggest that changes in frequency discrimination abilities of older adults may be, in part, related to changes in preattentive levels of auditory processing.

Age-Related Differences in Sensitivity of Peripheral Blood Monocytes to Lipopolysaccharide and Staphylococcus Aureus Toxin B in Atopic Dermatitis

As shown by atopy patch tests, atopic dermatitis (AD) is dominated in its acute phase by the development of a specific T(H)2 response after exposure of the skin to common environmental antigens. Relying on our previous data showing that Staphylococcus aureus enterotoxin B (SEB) induced the activation of monocyte-derived dendritic cells (DCs) through Toll-like receptor (TLR)2 and that SEB-pulsed DCs commit allogenic naive T cells into T(H)2, we assessed monocytes sensitivity to SEB and lipopolysaccharide (LPS) in a group of children and adult patients with AD. Monocytes from AD patients (15 adults with mostly severe disease and 15 children with mild to moderate disease) exhibited an activated and tolerant state as supported by (i) secretion of large amounts of IL-6, IL-10, and tumor necrosis factor-alpha even in the absence of stimulation; (ii) their inability to modulate neither HLA-DR and CD54 nor TLR2 and TLR4 expression after in vitro challenge with SEB; (iii) inhibition of IL-12p70 secretion in response to LPS. Interestingly, monocytes from some of the children studied responded to in vitro challenge with LPS, suggesting new hypotheses to explain disease regression. Our data support the notion that monitoring sensitivity of monocytes to bacterial toxins could prove useful to assess disease progression and prognosis in AD.

Comparative effects of oral chlorpyrifos exposure on cholinesterase activity and muscarinic receptor binding in neonatal and adult rat heart

Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M 2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M 2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor-mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M 2 receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age-related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac cholinesterase (ChE) activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1× LD 10: neonates, 7.5 and 15 mg/kg; adults, 68 and 136 mg/kg). Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1× LD 10, relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (≈30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e ., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC 50 values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that differential A-esterase activity was not responsible for the age-related difference in cholinesterase sensitivity between age groups. Pre-incubation of neonatal and adult tissues with selective inhibitors of AChE and butyrylcholinesterase (BChE) indicated that a majority (82–90%) of ChE activity in the heart of both neonates and adults was BChE. The rapid onset (by 4 h after dosing) of changes in muscarinic receptor binding in adult heart may be a reflection of the more potent direct binding to muscarinic receptors by chlorpyrifos oxon previously reported in adult tissues. The results suggest that ChE activity (primarily BChE) in neonatal heart may be inherently more sensitive to inhibition by some anticholinesterases and that toxicologically significant binding to muscarinic receptors may be possible with acute chlorpyrifos intoxication, potentially contributing to age-related differences in sensitivity.