Terry, Leslie M.

The effects of cocaine exposure and maternal deprivation on subsequent voluntary ingestion of cocaine and amphetamine was investigated in 7-day-old rat pups in order to further our understanding on the development of drug addiction. Maternally deprived and non-deprived pups were pre-exposed to a cocaine solution masked with 5% orange Tang solution. Four hours later, experimental pups were tested for subsequent cocaine self-administration (SA) (Exp. 1) or amphetamine SA, (Exp. 2), following a second deprivation period. Control pups were not deprived during this interval. Pups in both experiments were assessed for dose self-administered and for general activity. Results indicate that cocaine pre-exposure increased cocaine and amphetamine SA, and activity significantly increased after pre-exposure and testing sessions. Lastly, sensitization of the motor effects of cocaine was observed in pups pre-exposed to cocaine. This study provides a potential drug SA animal model not yet investigated in developing animals.

Cocaine use during pregnancy has been associated with neurobehavioral and cognitive difficulties in infants and toddlers. The present study used an elicited imitation procedure to investigate memory for sex-typed event sequences in preschool children. Measures of immediate and delayed recall was assessed in three groups of children: drug-exposed, at-risk, and not-at-risk. Results indicated that (1) drug-exposed males showed no evidence of demasculinization and/or feminization, (2) drug-exposed children, in general, did not recall a fewer number of different target acts or fewer actions in the correct order than the at-risk or not-at-risk children, and (3) drug-exposed and at-risk children exhibited a greater number of repetition errors and novel errors than not-at-risk children. Findings suggest that certain effects of prenatal drug exposure are still evident in children of preschool age.

This study was designed to develop an animal model of Attention Deficit Hyperactivity Disorder based on frontal cortical functioning in 3, 6, 9, & 12-day-old neonatal rats. In Expt. 1, frontal cortical activity was suppressed with intracranial injections of lidocaine, a local anesthetic. In Expt. 2, frontal activity was suppressed with brain transections. Pups in both experiments were tested in a habituation-to-odor learning paradigm and behaviors including general activity, headwaving, probing, and rolling were recorded. Results indicated that frontal cortical suppression, caused by either lidocaine injection or brain transection, resulted in significantly higher activity levels in 3-day-olds particularly with regard to rolling, suggesting that the frontal cortex is involved in the regulation of rolling behavior. Frontal transections, but not lidocaine injections, also significantly increased activity in 12-day-old pups due to increased locomotor probing and wall climbing. Results are consistent with the neuropsychological research regarding frontal cortical functioning and inhibition in children with ADHD, and show potential as a future animal model of ADHD.

This paradigm evaluated a novel chronic stressor paradigm that could be as effective as 24 hr of maternal deprivation (24-MD), yet be intrinsically capable of examination over numerous days in pre-weanling pups. It was hypothesized that a 19 hr chronic variable stressor paradigm (19-CVS) would be equally or more effective in eliciting a corticosterone (CORT) response than 24-MD and that 19-CVS would have elevated recovery CORT levels over 24-MD. The results indicated that (1) 19-CVS elicited a significantly greater CORT response than 24-MD immediately after stressor exposure and (2) 19-CVS had significantly elevated recovery CORT in comparison to 24-MD. These results demonstrate that 19-CVS early in development is capable of robustly activating the hypothalamic-pituitary-adrenal (HPA)-axis immediately after exposure and may prove useful as an early life stressor. However, additional work is necessary to clarify how these two distinct stressors differ in termination of their respective HPA response.

Rapid Eye Movement (REM) sleep in adult and neonatal mammals is characterized by episodes of high variability and bursting in brainstem sites associated with spontaneous tonic and phasic behavioral events such as REMs, nuchal inactivity and twitches of the body. REM sleep is the principal behavioral state during fetal and neonatal life and as has been demonstrated by various REM deprivation procedures to be indispensable during this period and to lead to long lasting behavioral defects in adult life. The guiding hypothesis throughout this dissertation is that the variability of REM-associated nuchal atonia episodes and other spontaneous motor events reflects the fractal time patterns of a global fetal REM sleep state over multiple timescales serving as a transient behavioral ontogenetic adaptation to changing developmental environments. Further, spontaneous activity over many levels of organization, including phasic REM motor activity during ontogeny, could play a fundamental role in the development of appetitive behavioral processes (e.g., searching and orienting) and other forms of neuroplasticity (e.g., learning and dynamic regulation of receptor fields and maps). The nature of this variability was investigated by measuring the durations of nuchal atonia over extended periods in fetal sheep and neonatal rats, species which are in a REM sleep-like state >50% of the time. Hurst's rescaled range analysis, which affords comparisons between natural time series with short- and long-term correlated fluctuations, indicated that variability in both species over short time scales is statistically similar to longer time scales (i.e., is fractal in time) and remarkably stable over the developmental periods examined. Spontaneous nuchal events in both species were also found to be described by convolutionally stable self-similar Levy distributions, suggesting that activity associated with fetal REM sleep could provide a stable, scale invariant source of correlated stimulation, facilitating integration of new neural changes into developing motor and cortical networks over gestation. These fractal time descriptions of spontaneous prenatal behaviors have implications for conceptualizing the evolutionary mechanisms underlying heterochrony (shifting self-affine relationships between the timing of gene expression and behavioral activity) and the plasticity essential to the genesis of behavioral neophenotypes.