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Linda Patia Spear

Publications and source records attributed to Linda Patia Spear.

10 recordsLinked to original sources
PubMed2006

Assessment of adolescent neurotoxicity: rationale and methodological considerations.

This introduction to the special issue of Neurotoxicology and Teratology on "Risk of neurobehavioral toxicity in adolescence" begins by broadly considering the ontogeny and phylogeny of adolescence, and the potential value of animal models of adolescence. Major findings from the emerging neuroscience of adolescence are then highlighted to establish the importance of studies of adolescent neurotoxicity. A variety of methodological issues that are of particular relevance to adolescent exposures are then discussed. These include consideration of pharmacokinetic factors, inclusion of other-aged comparison group(s), and issues involving timing, route of administration, and exposure-induced alterations in growth rate. Despite such methodological challenges, research to determine whether adolescence is a time of increased vulnerability (or greater resiliency) to specific drugs and environmental toxicants is progressing rapidly, as exemplified by the work presented in the articles of this special issue.

Adolescent↗
PubMed2006

Effects of acute ethanol or amphetamine administration on the acoustic startle response and prepulse inhibition in adolescent and adult rats.

RATIONALE: Adolescents differ from adults in their sensitivity to a variety of psychoactive drugs. For example, adolescent rats are less sensitive to locomotor stimulant and stereotypic effects of amphetamine as well as to motor-impairing and hypnotic effects of ethanol while more sensitive to ethanol-induced disruption of brain plasticity. OBJECTIVE: The current study further explored age differences in psychopharmacological sensitivity by examining the effects of d-amphetamine (1.0 and 4.0 mg/kg) or ethanol (0.5, 1.0 and 1.5 g/kg) given interperitoneally on the acoustic startle response (ASR) and prepulse inhibition (PPI) in male adolescent and adult Sprague-Dawley rats. MATERIALS AND METHODS: The animals were given five startle trials (120 dB for 40 ms) before semi-randomized presentation of 12 startle trials interspersed with ten trials at each prepulse intensity (40 ms pulse of 5, 10, or 20 dB above background; 100 ms before the startle stimulus). RESULTS: Adolescent controls showed significantly less PPI than adults, replicating previous ontogenetic findings. The higher dose of amphetamine disrupted PPI in adult but not in adolescent animals, extending previous reports of an adolescent insensitivity to amphetamine to include this measure of sensorimotor gating. Ethanol exposure failed to alter PPI at either age, although both the 1.0 and 1.5 g/kg doses of ethanol significantly suppressed the magnitude of the ASR at both ages, potentially reflecting sedative or anxiolytic effects. CONCLUSION: These data provide further evidence of the relative insensitivity of adolescent animals to amphetamine, although no age effects were found in terms of ethanol sensitivity using these measures of startle and sensorimotor gating.

Age Factors↗
PubMed2005

Adolescence. Alcohol sensitivity, tolerance, and intake.

Research conducted in laboratory animals has shown adolescents to be less sensitive to numerous ethanol effects that may serve as cues to limit intake, including effects evident during intoxication (e.g., ethanol-induced motor impairment, anxiolysis, social impairment, and sedation), as well as during the post-intoxication period (e.g., "hangover"-associated anxiogenesis). Conversely, adolescents are more sensitive than adults to a few ethanol effects, including ethanol-induced social facilitation and impairments in hippocampal long-term-potentiation. These age-specific ethanol sensitivities are not simply related to developmental differences in ethanol pharmacokinetics. Instead, they appear related in part to an ontogenetic decline in expression of within session (acute) tolerance and to differential rates of development of neural systems underlying different actions of ethanol. Relatively high levels of ethanol intake often seen in adolescent rodents and their human counterparts may be related not only to an attenuated sensitivity of adolescents to negative cues that normally serve to limit drinking, but also their greater sensitivity to both the facilitation of social behavior by ethanol and the stimulation of ethanol intake by social experiences. Although data are sparse, studies in laboratory animals hint that under some circumstances chronic adolescent exposure to ethanol may influence ongoing neural maturation and later neural, cognitive, and behavioral functioning, including later sensitivity to and propensity to use ethanol. Recommendations for further research are discussed.

Adolescent↗
PubMed2004

Characterizing the ontogeny of ethanol-associated increases in corticosterone.

The following experiments were conducted as adjuncts to previous work in an effort to characterize the ontogenetic profile of the elevations in corticosterone after ethanol challenge. In Experiment 1, female and male Sprague-Dawley rats were administered intraperitoneally either a 1.5- or a 4.5-g/kg dose of ethanol on postnatal day (PND) 16, 26, 36, or 56. Blood samples were collected at 40, 80, or 160 min after ethanol injection and analyzed by means of radioimmunoassay for corticosterone levels and correlated with brain alcohol levels (BrALs) determined from brain samples collected at the same time intervals. In Experiment 2, the ethanol dose was varied ontogenetically to equate functional impairment across age, with the use of intraperitoneal doses of ethanol of 3.2, 2.6, or 2.2 g/kg, to induce equivalent amounts of ethanol-induced motor impairment in infant (PND 22), adolescent (PND 28), or adult (PND 60) rats, respectively. Animals were tested on a swim task 15 min after injection, with blood and brain samples collected immediately after the swim and analyzed for corticosterone levels and BrALs as in Experiment 1. Reminiscent of previous reports of an age-related increase in sensitivity to the hypnotic and motor-impairing effects of ethanol, the corticosterone response to an ethanol challenge increased at least through adolescence, with sex differences emerging by PND 26 and becoming more pronounced in adulthood. To the extent that corticosterone release is involved in the reinforcing effects of drugs, ontogenetic differences in the response of the hypothalamic-adrenal-pituitary (HPA) axis to ethanol could contribute to the excessive alcohol consumption often observed during adolescence.

Age Factors↗
PubMed2004

Adolescent brain development and animal models.

Research examining brain development during adolescence is escalating rapidly along multiple dimensions, as illustrated by the remarkable diversity of trans-disciplinary work shown in this symposium. Ontogenetic transitions characteristics of adolescence are common among mammalian species. Although no other species demonstrates the full complexity of brain and behavioral function seen in human adolescents, adolescence appears to be a highly conserved developmental stage, its characteristics sculpted to meet common evolutionary pressures that include the avoidance of inbreeding at this time of sexual emergence. Numerous similarities are found between human adolescents and adolescents of other species in terms of developmental history and genetic constraints, as well as neurobehavioral and physiological characteristics. These similarities provide face and construct validity to support use of animal models as tools for the study of adolescence and the unique opportunities and vulnerabilities afforded by this developmental transition.

Adolescent↗
PubMed2004

Adolescence and the trajectory of alcohol use: introduction to part VI.

Research in the area of adolescent alcohol use is progressing rapidly, as exemplified by the chapters in this section. Basic animal research in rodents has revealed adolescents to be more sensitive than adults to ethanol-induced disruptions in brain plasticity, although adolescents conversely are relatively insensitive to ethanol cues that serve to moderate intake. Risks for excessive alcohol consumption due to genetic background have been shown in primate research to be exacerbated by adverse early life experiences. Studies in clinical populations have revealed neurocognitive deficits evident years following adolescent alcohol abuse, along with evidence that some neural changes may predate adolescent alcohol abuse, whereas others appear to be a consequence of this abuse. Further research is needed to detail determinants and consequences of adolescent alcohol abuse and to identify potential protective factors to diminish the propensity for excessive use of alcohol during this critical developmental period.

Adolescent↗
PubMed2004

Age-related differences in elevated plus maze behavior between adolescent and adult rats.

Adolescence is a time of considerable transformations, often associated with increases in risk taking and novelty-seeking behaviors. Little is known of a possible age-dependent expression of anxiety-related behaviors in novel or potentially dangerous situations. The present study explored age differences in anxiogenic and anxiolytic stimuli between adolescent and adult Sprague-Dawley rats using the elevated plus maze (EPM). Data were compared across several experiments using factor analysis of multiple EPM measures. Under some circumstances, adolescents revealed a relatively low behavioral anxiety profile compared to adults, whereas in other situations results revealed the opposite pattern. Characteristics of the pretest circumstances altered considerably the nature of the conclusions reached regarding age-related changes in anxiogenic and anxiolytic stimuli. In general, anxiety measures in adolescents were less affected by variations in pretest conditions compared to the same variables in adults, suggesting possible adolescent immaturity of brain mechanisms involved in the regulation of anxiety.

Age Factors↗
PubMed2003

Anxiogenic effects during withdrawal from acute ethanol in adolescent and adult rats.

Elevated signs of anxiety are observed in adult rodents during withdrawal from chronic as well as acute ethanol exposure. To determine whether adolescents, in addition to their insensitivity to a number of acute ethanol effects, might likewise be hyposensitive to these anxiogenic manifestations of withdrawal from an acute ethanol challenge, the behavior of adolescent and adult male Sprague-Dawley rats was assessed in an elevated plus maze (EPM) 18 h following intraperitoneal challenge with 4 g/kg ethanol. Adult but not adolescent animals demonstrated evidence of anxiety in the plus maze during acute ethanol withdrawal. To ensure that this finding did not merely reflect age differences in ethanol clearance, clearance times at each age were determined, with additional adolescents tested at the same time postclearance as the adults were previously. Adolescents still failed to demonstrate anxiogenic signs of withdrawal. Suppression of activity during the withdrawal test, however, was evident in animals of both ages. A relative resistance to the anxiogenic effects associated with acute ethanol withdrawal during adolescence could serve as a permissive factor for development of binge drinking patterns among human adolescents.

Aging↗
PubMed2002

The adolescent brain and the college drinker: biological basis of propensity to use and misuse alcohol.

OBJECTIVE: This article reviews the literature on adolescent brain development and considers the impact of these neural alterations on the propensity to use and misuse alcohol. METHOD: Neural, behavioral and hormonal characteristics of adolescents across a variety of species were examined, along with a review of the ontogeny of ethanol responsiveness, tolerance development and stress/alcohol interactions. RESULTS: The adolescent brain is a brain in transition. Prominent among the brain regions undergoing developmental change during adolescence in a variety of species are the prefrontal cortex and other forebrain dopamine projection regions, stressor-sensitive areas that form part of the neural circuitry modulating the motivational value of alcohol and other reinforcing stimuli. Along with these characteristic brain features, adolescents also exhibit increased stressor responsivity and an altered sensitivity to a variety of ethanol effects. Findings are mixed to date as to whether exposure to ethanol during this time of rapid brain development alters neurocognitive function and later propensity for problematic ethanol use. CONCLUSIONS: Developmental transformations of the adolescent brain may have been evolutionarily advantageous in promoting behavioral adaptations to avoid inbreeding and to facilitate the transition to independence. These brain transformations may also alter sensitivity of adolescents to a number of alcohol effects, leading perhaps in some cases to higher intakes to attain reinforcing effects. These features of the adolescent brain may also increase the sensitivity of adolescents to stressors, further escalating their propensity to initiate alcohol use. Additional investigations are needed to resolve whether ethanol use during adolescence disrupts maturational processes in ethanol-sensitive brain regions.

Adolescent↗