Biomedical subjects

L P Spear

Publications and source records attributed to L P Spear.

At least 19 recordsLinked to original sources

PubMed2004

The effects of NMDA and GABAA pharmacological manipulations on acute and rapid tolerance to ethanol during ontogeny.

BACKGROUND: Sensitivity to several ethanol effects increases during ontogeny, perhaps in part because of a notable decline in acute tolerance. In contrast, rapid tolerance to ethanol-induced sedation emerges slowly during ontogeny. This study tested the hypothesis that ontogenetic differences in glutamate and/or gamma-aminobutyric acid systems influence tolerance expression. METHODS: Sprague-Dawley rats at postnatal day (P)26 or P70 received (+)MK-801, muscimol, or saline before ethanol (3.5 or 4.5 g/kg) or saline on day 1 and ethanol only on day 2. Loss of and time to regain the righting reflex and blood alcohol levels at recovery were recorded. The presence of acute tolerance was indicated as a positive slope of the linear regression of blood alcohol levels at recovery versus ethanol dose. Rapid tolerance was estimated on day 2 by comparing animals given ethanol only on day 2 with those given ethanol on both days. RESULTS: Acute tolerance on day 1 only was observed at P26; this was disrupted by (+)MK-801 but not muscimol. Evidence for acute tolerance also emerged in adults on day 2. Whereas both drugs increased ethanol sedation at both ages, they did not facilitate ontogenetic expression of rapid tolerance: rapid tolerance was not evident at P26 regardless of pretreatment when indexed in terms of recovery time. CONCLUSIONS: These data provide further evidence for an ontogenetic dissociation in the expression of acute and rapid tolerance to ethanol-induced sedation. Pharmacological attenuation of the expression of acute tolerance was sufficient but not necessary to delay recovery of righting after ethanol. The greater propensity of young animals to develop acute tolerance, seemingly modulated in part by NMDA receptors, may contribute to their relative resistance to ethanol, although other factors, including pharmacokinetic factors, also contribute to their more rapid recovery from ethanol sedation.

Aging↗

PubMed2004

The effects of ethanol on spatial and nonspatial memory in adolescent and adult rats studied using an appetitive paradigm.

Adolescent rats have been reported to be less sensitive than adults to many acute ethanol effects, including ethanol-induced sedation and motor impairment, but conversely more sensitive to ethanol-induced disruptions in spatial memory in a Morris water maze (Markwiese et al., 1998). The present study examined adolescent and adult rats trained for 6 days under spatial or nonspatial versions of a presumably less stressful sand box maze. Moderately food-deprived animals were given 0, 0.5, or 1.5 g/kg ethanol intraperitoneally 30 min before training each day, but were tested without ethanol or reinforcer on test day. Spatial acquisition was impaired by 1.5 g/kg in adults but not adolescents, with no ethanol impairment on the nonspatial task at either age. These results are opposite the ontogenetic profile reported by Markwiese et al., (1998) and may reflect differential activation of prefrontal cortex or other stress-sensitive forebrain regions by the two tasks across age.

Age Factors↗

PubMed2004

Adolescent ethanol sensitivity: hypothermia and acute tolerance.

A two-injection paradigm was used to assess acute (within-session) tolerance to ethanol in telemetry-implanted adolescent and adult rats. Male rats were intragastrically pretreated with either 1.0 g/kg of ethanol or water and then challenged with 2.0 g/kg of ethanol or water when blood alcohol levels (BALs) of ethanol-pretreated animals were anticipated to approach zero. Adults showed more rapid and sustained ethanol-induced hypothermia than adolescents. Acute tolerance to ethanol-induced hypothermia did not emerge clearly with the two-injection paradigm; ethanol-pretreated animals of both ages generally did not differ from those pretreated with water in their hypothermic response to ethanol despite higher BALs after the second intubation. Housing condition (paired or isolated) had little influence on ethanol-induced hypothermia. The adolescent attenuation of ethanol-induced hypothermia in this experiment was not associated with greater expression of within-session (acute) tolerance.

Age Factors↗

PubMed2002

The effects of NMDA and GABAA pharmacological manipulations on ethanol sensitivity in immature and mature animals.

BACKGROUND: Sensitivity to the hypnotic effects of ethanol dramatically increases with age (Silveri and Spears, 1998). Little is known regarding the neural mechanisms that might underlie this relative resistance of young animals to ethanol. The present study used a psychopharmacological approach to examine the influence of NMDA (N-methyl-D-aspartate) and GABA (gamma-Aminobutyric acid) receptor systems in modulating age differences in ethanol responsiveness between young [postnatal day (P26)] and mature (P70) female and male Sprague-Dawley rats. METHOD: Dose response curves were established for the effects of intraperitoneal (ip) administration of the NMDA antagonist (+)MK-801 (0.75, 1.0, or 1.25 mg/kg), the GABAA agonist muscimol (0.75, 1.25, or 1.75 mg/kg), or saline on loss and regain of the righting reflex and trunk blood alcohol levels following 3.5 g/kg of ethanol. RESULTS: (+)MK-801 increased time to regain the righting reflex at both ages, maintaining the age-related increase in ethanol sensitivity typically observed, although a gender effect also emerged at P70, with females being more sensitive than males to (+)MK-801-induced increases in duration of loss of the righting reflex. In contrast to the across-age similarity in responsiveness to (+)MK-801, P26 animals were considerably more sensitive to muscimol's enhancing effect on ethanol sedation than mature animals. CONCLUSION: Although modulation of either the NMDA or GABA system enhances the sedative effects of ethanol at both ages, stimulation of the GABAA receptor is a more effective means of prolonging ethanol sedation in immature than mature animals.

Age Factors↗

PubMed2001

Acute effects of ethanol on behavior of adolescent rats: role of social context.

BACKGROUND: First experiences with alcohol in humans occur predominantly in adolescence, and to a large extent the attractiveness of alcohol at this age is based on its ability to facilitate certain forms of social behavior (social facilitation). Adolescence is strongly marked by a focus on peer relationships, and the social nature of the situation plays an important role in responsiveness to alcohol. Peer-directed social activity of adolescent rats may be a valuable experimental model for the study of ethanol-induced changes in social behavior and assessment of the role of the social context in responsiveness to ethanol. METHOD: In the present study we used a modified dyad social interaction test to characterize acute effects of ethanol on different forms of social behavior (social investigation, contact behavior, and play) and social motivation (preference/avoidance of a peer) in adolescent rats. Ethanol effects on behavior directed toward a peer were compared with those induced by exposure to an inanimate novel object. RESULTS: In the social context, the effects of ethanol were dose-dependent and biphasic. Low doses of ethanol (0.25-0.75 g/kg) produced apparent social facilitation (increased social activity and enhanced social preference), whereas higher doses (3 and 4 g/kg) caused social inhibition (decreased social activity and avoidance of a peer). This pattern was not observed for a nonsocial stimulus: Although overall activity in the nonsocial context was suppressed by 2 and 3 g/kg of ethanol, 0.5 g/kg of ethanol did not activate overall activity directed to the inanimate object. CONCLUSIONS: These findings demonstrate that the social nature of the testing situation plays an important role in responsiveness to alcohol in adolescence, especially to its activating effects. The results suggest also that the study of ethanol effects on social behavior of adolescent rats may be an effective tool for the study of adolescent alcohol use and abuse.

Age Factors↗

PubMed2001

Ethanol as a reinforcer in the newborn's first suckling experience.

BACKGROUND: Recent evidence suggests that human infants prefer alcohol-flavored milk when fed through a bottle. Animal models also indicate a surprising predisposition for neonatal and infant rats to voluntarily and willingly ingest ethanol. These findings suggest high susceptibility to the reinforcing properties of ethanol early in ontogeny. METHODS: A surrogate nipple technique-a highly effective tool for investigation of the reinforcing properties of different fluids-was applied in the present study. Tests of ethanol reinforcement were accomplished in terms of two basic paradigms of Pavlovian conditioning. In one paradigm, the conditioned stimulus (CS) was the surrogate nipple, and in the other, the CS was a novel odor. RESULTS: Newborn rats showed sustained attachment to the nipple providing 5% ethanol, and later reproduced this behavioral pattern toward the empty nipple (CS alone). Ingestion of ethanol yielding appetitive reinforcement was accompanied by detectable blood alcohol concentrations, with most in the range of 20-30 mg/dl. The reinforcing efficacy of ethanol was also confirmed in the classical olfactory conditioning paradigm: following pairing with intraoral ethanol infusions, the odor (CS) alone elicited sustained attachment to an empty nipple. Females showed better olfactory conditioning with low concentrations of ethanol, whereas males were effectively more conditioned to high concentrations. Although there were no reinforcing consequences of intraperitoneally injected ethanol [as an unconditioned stimulus (US)] when a neutral odor was the CS, when paired with ingestion of water from a nipple, the injection of ethanol had a reinforcing effect. CONCLUSIONS: The present series of experiments revealed ethanol reinforcement in the newborn rat. Two varieties of Pavlovian conditioning established that ethanol can serve as an effective US, and hence reinforcer, in such a way as to increase the approach and responsiveness toward stimuli paired with that US, indicating appetitive reinforcement.

Animals↗

PubMed2001

Acute, rapid, and chronic tolerance during ontogeny: observations when equating ethanol perturbation across age.

BACKGROUND: Sensitivity to the motor-impairing and hypnotic effects of ethanol (EtOH) increases notably during development. Less is known, however, about the ontogeny of EtOH tolerance and the ontogenetic relationship among different types of tolerance. Consequently, we compared the ontogenetic development of acute, rapid, and chronic tolerance to EtOH-induced motor impairment and hypothermia in a swim task. METHODS: Preweanling, adolescent, and adult female and male Sprague-Dawley rats were given chronic saline (control group), five daily EtOH exposures before EtOH on test day (chronic group), one EtOH exposure before test day (rapid group), or EtOH exposure only on test day (acute groups). Separate groups of animals in the acute groups were tested at 15, 60, or 105 min after injection to estimate acute tolerance development via calculating slopes of the linear regression of impairment relative to brain alcohol levels at each postinjection interval. Initial EtOH perturbation of swim performance was equated across age by varying EtOH dose. RESULTS: Acute tolerance was evident to the motor-impairing effects of EtOH at all ages. When impairment was indexed relative to brain alcohol levels, rapid and chronic tolerance to the motor-impairing effects of EtOH on latency to reach the start was seen across age, although this tolerance tended to be more pronounced in adults. Somewhat different ontogenetic patterns of tolerance development were observed with EtOH-induced hypothermia, a dependent measure for which EtOH perturbation was not equated across age. CONCLUSIONS: The degree of initial perturbation by EtOH seems to be an important predictor of tolerance expression during ontogeny. That is, ontogenetic profiles of tolerance development differ significantly when EtOH-induced motor impairment is equated across age rather than dose of EtOH administered. The role of target response measures and context stress should also be considered when exploring ontogenetic expression of EtOH tolerance.

Aging↗

PubMed2000

Cocaine and morphine-induced place conditioning in adolescent and adult rats.

The periadolescent period in the rat is characterized by alterations in novelty seeking and exploratory behavior, as well as changes in the behavioral responsiveness to many drugs of abuse. These alterations may be predictive of alterations in the reward value of drugs of abuse. The present experiments examined whether adolescent rats (34-37 days old) differ from their adult counterparts in the expression of drug-induced place conditioning for morphine (0, 2.5, or 5 mg/kg; Experiment I) and cocaine (0, 5, or 10 mg/kg; Experiments II and III). Animals received multiple conditioning days, followed 24 h later by a drug-free CPP test. All drugs were given intraperitoneally immediately prior to confinement in the CS+ compartment, while vehicle injections were given prior to exposure to the CS- chamber. For both drugs, there were no significant differences between adolescents and adults in amount of place conditioning seen when drug exposure was paired with the nonpreferred chamber. When cocaine was paired with either the preferred or nonpreferred compartment (Experiment III), again, the magnitude of the place conditioning observed did not differ between adolescents and adults. The lack of age differences in expression of drug-induced place conditioning in the present experiments is not likely a result of ceiling effects, because the data suggest that the doses used included near-threshold doses. Although these findings need to be confirmed using other approaches for assessing drug reward before concluding that adolescent and adult rats exhibit similar sensitivity to the rewarding effects of morphine and cocaine, the current data revealed no differences between adolescents and adults in the magnitude of place conditioning expressed for morphine or cocaine.

Aging↗

PubMed2000

The adolescent brain and age-related behavioral manifestations.

To successfully negotiate the developmental transition between youth and adulthood, adolescents must maneuver this often stressful period while acquiring skills necessary for independence. Certain behavioral features, including age-related increases in social behavior and risk-taking/novelty-seeking, are common among adolescents of diverse mammalian species and may aid in this process. Reduced positive incentive values from stimuli may lead adolescents to pursue new appetitive reinforcers through drug use and other risk-taking behaviors, with their relative insensitivity to drugs supporting comparatively greater per occasion use. Pubertal increases in gonadal hormones are a hallmark of adolescence, although there is little evidence for a simple association of these hormones with behavioral change during adolescence. Prominent developmental transformations are seen in prefrontal cortex and limbic brain regions of adolescents across a variety of species, alterations that include an apparent shift in the balance between mesocortical and mesolimbic dopamine systems. Developmental changes in these stressor-sensitive regions, which are critical for attributing incentive salience to drugs and other stimuli, likely contribute to the unique characteristics of adolescence.

Aging↗

PubMed2000

Ontogeny of ethanol elimination and ethanol-induced hypothermia.

Ontogeny of ethanol elimination rates and ethanol-induced hypothermia were examined as possible mechanisms contributing to the marked reduction in ethanol sensitivity early in life (Little et al., 1996; Silveri & Spear, 1998) and the notable gender difference in ethanol sleep-time seen in adult animals (Silveri & Spear, 1998). Elimination rates and brain/blood ethanol levels were determined following doses of 1.5 or 4.5 g/kg ethanol in male and female Sprague-Dawley rats at postnatal days (P)16, 26, 36, or 56. Animals were sacrificed at 40, 80, or 160 min post-injection, with ethanol elimination rates estimated from the slope of the regression of blood and brain alcohol levels across the three sampling periods. P16 animals exhibited the slowest rate of ethanol metabolism, while no gender effects were evident at any age. Observed ontogenetic increases in ethanol hypothermia were not systematically related to the ontogeny of ethanol metabolism. Factors other than ontogenetic changes in ethanol metabolism, hypothermia, or the distribution of ethanol between brain and blood must underlie the relative insensitivity to ethanol often reported in young and adolescent organisms, a fruitful area for future studies given the frequent use and misuse of alcohol by human adolescents.

Age Factors↗

PubMed2000

Acute effects of ethanol and the first suckling episode in the newborn rat.

BACKGROUND: In humans, early postnatal experience with alcohol is far from rare and includes exposure to alcohol through breast milk or through the bottle to attain sedative effects (Croce, 1987). Exposure to alcohol though mother's milk alters the infant's suckling behavior. However, acute effects of alcohol on suckling behavior using animal models remain to be investigated. METHODS: The present study was designed to examine the effects of neonatal alcohol exposure on attachment to a surrogate nipple and ingestion of milk in rat pups, naive both to suckling and to maternal care. Cesarean-delivered rat pups were pre-exposed to four dosages of ethanol (0, 1, 2, and 3 g/kg intragastrically) and tested 30 min after ethanol administration. RESULTS: Suckling behavior was impaired only in pups exposed to a dosage of 3 g/kg of ethanol. Pups in this group demonstrated longer latency to attach followed by less efficient suckling--the pups maintained contact with the nipple but showed decreased ingestion of milk from it. Pups treated with 1 g/kg of ethanol showed the greatest suckling efficiency, ingesting far more milk per minute attached to the surrogate nipple than pups in all other groups. At the same time, nonevoked motor activity was significantly suppressed by all three dosages of ethanol. Blood alcohol levels showed a linear relationship with dose at 30 min postintubation. CONCLUSIONS: These findings suggest a dissociation between acute ethanol effects on suckling and overall motor activity, with suckling apparently less sensitive to suppressive and more sensitive to activating effects of ethanol.

Animals↗

PubMed1999

Effects of early handling on amphetamine-induced locomotor activation and conditioned place preference in the adult rat.

RATIONALE: Altered hormonal stress responsiveness has been implicated in psychostimulant responsivity, and early handling represents a mild environmental manipulation which alters the hormonal profile following stress exposure. OBJECTIVE: The present experiments examined whether early handling in rats would alter locomotor effects of amphetamine, as well as cross-sensitization of locomotor responsiveness after chronic stress. Conditioned place preference (CPP) for amphetamine was also measured. METHODS: Handling consisted of daily 15-min isolation periods from days 1-12 postnatally. Novelty- and amphetamine (0, 1.5 mg/kg)-induced locomotion were examined using circular corridors in adult rats that were either restrained repeatedly over 8 days or not disturbed prior to testing. The effects of handling on amphetamine (0, 1, 2, 5 mg/kg) conditioned place preference (CPP) were also examined following 3 days of drug-compartment pairings. RESULTS: Early handling produced a more rapid post-stress recovery in corticosterone levels. Handled animals also exhibited a significant attenuation in amphetamine-induced CPP compared to non-handled controls. Locomotor responsiveness to novelty and amphetamine was not altered by early handling. Although no cross-sensitization was observed, evidence for stress sensitization was seen, but was unaffected by early handling. CONCLUSIONS: Handled animals showed an attenuated CPP for amphetamine, data suggesting that sensitivity to the reward value of drugs of abuse in adulthood may be susceptible to relatively minor environmental manipulations early in life. This effect of handling on CPP does not seem to reflect differences in locomotor sensitivity to amphetamine.

Amphetamine↗

PubMed1999

Social behavior and social motivation in adolescent rats: role of housing conditions and partner's activity.

The present study investigated 1) the effects of individual and grouped housing on social investigation, social contact behavior, and play behavior in adolescent rats tested with low socially active (grouped) and high socially active (isolated) play partners; and 2) the effects of long-term (8 days) and short-term (24 h) isolation on social behavioral manifestations and social motivation in terms of preference or avoidance of play partners. Social isolation of adolescent rats activated play behavior and social behaviors different from play, but play was predominantly affected under the conditions of this study. Long-term isolation was more effective than short-term, and resulted in greater manifestation of play and social preference. Adolescent rats were able to modify their social behaviors in response to social activity of the play partner: in isolated animals exposed to low socially active group-housed partners, play behavior was transformed into social activities unrelated to play; exposure of group-housed adolescents to high socially active previously isolated partners resulted in an increase of play behavior. Testing that allowed avoidance of social contacts revealed a dissociation between manifestations of play behavior and social motivation: group-housed play partners of isolated animals showed elevated levels of play behavior but a tendency to avoid their isolated pairmates.

Aging↗

PubMed1999

Inhibition of nitric oxide synthesis with L-NAME suppresses isolation-induced ultrasounds in rat pups.

The present experiments examined the impact of manipulating the NO system on production of isolation-induced ultrasonic vocalizations (USVs) in 10- and 11-day-old rat pups. Pups were tested under both high- and low-baseline USV emission; the latter was accomplished by pretest administration of cocaine, a drug known to suppress USVs. Treatment with 10, 50, or 100 mg/kg (but not 1 mg/kg) of the nitric oxide synthase (NOS) inhibitor L-nitro-arginine methyl ester (L-NAME) significantly attenuated USV production, as did injection of 10 mg/kg cocaine; combined treatment with both drugs did not result in greater suppression, perhaps due to a floor effect. Although cocaine increased locomotor activity, treatment with L- or D-NAME alone did not alter activity levels. Exposure to L-NAME induced some hypothermia, although these alterations in body temperature were not systematically related to the drug-induced suppression of USVs. Alterations in USV production by L-NAME were not evident after pretreatment with the less active isomer D-NAME, evidence supporting the importance of NO synthesis inhibition per se in the marked L-NAME-induced suppression of USVs in isolated infant rats.

Analysis of Variance↗

PubMed1999

Schedule-induced polydipsia: gender-specific effects and consequences of prenatal cocaine and postnatal handling.

The impact of gestational cocaine in conjunction with postnatal handling on schedule-induced polydipsia (SIP) was examined. Rat offspring were derived from Sprague-Dawley dams injected subcutaneously with 40 mg/kg/3 cc cocaine hydrochloride (C40) on gestational days 8-20, dams injected with vehicle and pair fed 4 (PF4) days to mimic the acute anorexic effects of cocaine administration, and nontreated (NT) control dams. In adulthood, offspring were food deprived and given 13 daily 30-min SIP sessions, with water intake recorded during the scheduled (fixed time 60 s-FT60) food delivery. For 4 days thereafter, animals received saline, 5 or 10 mg/kg of cocaine in counterbalanced order prior to SIP testing. Acquisition and maintenance of SIP, but not cocaine-induced suppression of SIP performance, were observed to be dependent upon prenatal treatment, handling, and gender. Females acquired SIP faster and exhibited notably higher levels of polydipsia than males. Early handling increased levels of established SIP in NT offspring, while enhancing SIP acquisition in both PF4 and C40 offspring. In nonhandled animals, NT offspring exhibited less SIP than PF4 and C40 offspring, differences that were attenuated by early handling. These effects are discussed in relation to previously reported neurohormonal characteristics of these gender and treatment variables.

Analysis of Variance↗

PubMed1999

Ontogeny of rapid tolerance to the hypnotic effects of ethanol.

BACKGROUND: Alcohol use typically begins during adolescence. Little is known regarding the antecedents and impact of this early alcohol use, although age-related changes in the neural systems modulating alcohol sensitivity could contribute to the propensity of adolescents to consume alcohol. We have previously observed a marked ontogenetic decline in acute tolerance to ethanol (EtOH), with preweanling pups exhibiting the most acute tolerance (Silveri and Spear, 1998). The objective of this study was to assess whether rapid tolerance shows a similar ontogenetic profile. METHODS: In Experiment I of the present study, female and male Sprague-Dawley preweanling rats at postnatal day (P) 16 or young adults at P56 were examined. On Day 1, preweanlings were pretreated with saline, 1.5, 3.5, or 5.0 g/kg EtOH and adults were pretreated with saline or 3.5 g/kg EtOH. This was followed by challenge with 3.5 g/kg EtOH and assessment of ethanol-induced sleep time on Day 2. In Experiment II, adolescents at P36 were pretreated with saline, 3.5, or 5.0 g/kg EtOH on Day 1 before Day 2 assessment of sleep time after 3.5 g/kg EtOH. Upon awakening, animals were killed and whole brains removed and analyzed for brain alcohol levels (BrALs). RESULTS: Rapid tolerance was observed in P36 and P56 animals, with EtOH-pretreated animals exhibiting significantly shorter sleep times than age-matched animals treated with saline. In contrast, no evidence for rapid tolerance was seen after any pretreatment dose at P16. Interestingly, although EtOH-pretreated adults woke at higher BrALs than saline-treated adults, this pattern was not evident in the adolescents, which suggests that at this age, metabolic tolerance may play a prominent role in the expression of rapid tolerance. Thus, it seems as though the ability to develop rapid tolerance to EtOH hypnosis emerges during adolescence and continues into adulthood. CONCLUSIONS: Together with previous findings that adolescent animals also display substantial acute tolerance to alcohol (Silveri and Spear, 1998), the propensity of adolescents for developing these two forms of tolerance may have important implications for the increased voluntary consumption of alcohol at this age relative to other ages.

Age Factors↗

PubMed1999

Changes in progressive ratio responding for intravenous cocaine throughout the reproductive process in female rats.

Operant responding on a progressive ratio (PR) schedule for intravenous cocaine as well as sucrose reinforcement was examined in female rats throughout the reproductive process. Self-administration sessions began before mating, and continued throughout pregnancy and until lactational Day 8; following parturition, litters were present with dams during operant sessions. Physiological changes associated with the reproductive process dramatically altered PR responding for cocaine, while PR responding for sucrose was relatively stable throughout pregnancy and lactation. Female animals exhibited the highest number of responses/session for cocaine during estrus and the 1st trimester of pregnancy and the lowest responding near parturition, with levels only partially recovering during lactation. Dams self-administering cocaine exhibited notably different patterns of maternal behavior in the operant chambers than dams responding for sucrose. Thus, cocaine's reinforcing efficacy may be influenced by (a) the changing physiological profile associated with the reproductive process and (b) competition from the reinforcing properties of offspring during lactation.

Animals↗

PubMed1998

Animal behavior models. Increased sensitivity to stressors and other environmental experiences after prenatal cocaine exposure.

Neural compensations occurring after prenatal cocaine exposure may often permit some functional recovery, although the cost of this reorganization may be a decrease in adaptability. As we have seen in our rodent model of prenatal cocaine exposure, latent deficits may become unmasked when offspring are exposed to cognitive and environmental demands and stressors. In adolescence and adulthood, offspring exposed gestationally to cocaine exhibit characteristic decreases in stress-induced immobility along with increases in aggression under the demands of social competition. Recently, we observed that cocaine-exposed offspring are also unusually sensitive to the long-term effects of early manipulation (noninvasive heart rate testing at 16 days of age). When tested in adulthood, cocaine-exposed offspring not receiving this early experience exhibited less immobility when tested in the presence of intermittent footshock or when subsequently examined in an open field as well as more locomotion in the open field than control offspring, findings reminiscent of previous work. By contrast, these effects were normalized (shock-induced immobility) or reversed (open field immobility and locomotion) in cocaine-exposed animals given the early experience. This marked susceptibility to the effects of early manipulation was less evident in control offspring and even in a group of stunted nutritional controls. Thus, cocaine-exposed offspring may exhibit increased sensitivity not only to environmental demands and stressors, but also to the potential moderating or beneficial effects of early experiences.

Aging↗