Biomedical subjects

Cheryl L Kirstein

Publications and source records attributed to Cheryl L Kirstein.

9 recordsLinked to original sources

PubMed2006

Cocaine during adolescence enhances dopamine in response to a natural reinforcer.

The use of cocaine during adolescent development could alter the normal growth of brain regions affected by cocaine, specifically the reward system, and impact the adult mesolimbic system. However, there is scant literature aimed at determining whether animals are more vulnerable to the adverse effects of drugs during adolescence. The present study investigated whether cocaine pretreatment in either adolescence or adulthood altered the dopaminergic response to a naturally reinforcing substance in adulthood. To evaluate the responsivity of the mesolimbic system after repeated cocaine, sucrose was offered during the dialysis procedure and dialysates were collected. Regardless of age all saline pretreated rats had significant increases in sucrose-induced extracellular dopamine (DA) levels in the nucleus accumbens septi (NAcc) as compared to baseline levels. Rats pretreated with cocaine as adults also had significant increases in DA levels after sucrose. Interestingly, sucrose intake significantly enhanced DA levels in cocaine pretreated adolescent rats as compared to all other conditions. The results from the present study show that in rats pretreated with cocaine during adolescence there is an enhanced response of the dopaminergic system in animals exposed to a naturally reinforcing substance. Therefore, cocaine exposure during adolescence results in long-term functional changes in the mesolimbic pathway. Future studies need to ascertain the underlying mechanisms and their potential role in cocaine addiction.

Age Factors↗

PubMed2006

Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi.

In humans, adolescent exposure to illicit drugs predicts the onset of adult drug abuse and suggests that early drug use potentiates vulnerability to drug addiction. Cocaine conditioned place preferences were measured in early adolescent [postnatal day (PND) 35], late adolescent (PND 45) and young adult (PND 60) rats by injecting either 0, 5 or 20 mg/kg cocaine and conditioning them to environmental cues. Cocaine preferences were found for all ages at the high dose. PND 35s were the only age group to have a preference at the low dose. To address whether age-related differences in cocaine place preferences were related to differences in the mesolimbic dopaminergic system, we measured extracellular dopamine levels in the nucleus accumbens septi of PND 35, PND 45 and PND 60 rats via quantitative microdialysis under transient conditions. Rats were injected daily with either 5 mg/kg/ip or saline for 4 days and surgically implanted with a microdialysis probe aimed at the nucleus accumbens. Rats were perfused with either 0, 1, 10 or 40 nM dopamine and the extracellular dopamine concentration was measured. Our results show that adolescents differ from adults in basal dopamine. All cocaine treated rats, regardless of age, showed a significant increase in dopamine over baseline in response to a cocaine challenge. Additionally, there were age-related differences in the extraction fraction (E(d)), an indirect measure of dopamine reuptake. Together these findings suggest ontogenetic differences in extracellular dopamine and dopamine reuptake and that these differences may provide an explanation for adolescent vulnerability to addiction.

Aging↗

PubMed2006

Effects of novelty on behavior in the adolescent and adult rat.

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 novelty-induced 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.

Age Factors↗

PubMed2005

Neurochemical effects of cocaine in adolescence compared to adulthood.

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 novelty-induced 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.

Age Factors↗

PubMed2005

Cocaine-induced locomotor activity is increased by prior handling in adolescent but not adult female rats.

Adolescence is a period of transition that is associated with increased levels of stress and a heightened propensity to initiate drug use. Neuronal development is still occurring during this transitional period, which includes the continued development of the dopamine system during the adolescent period. In the present study, the effects of pre-test handling on cocaine-induced locomotor activity were investigated among female adolescent and young adult rats upon presentation to a novel environment. On postnatal days (PND) 41-44 and 56-59 animals were handled (b.i.d.) in the colony room for 3 min. On PND 45 or PND 60, animals were removed from the colony room, weighed, and administered an acute injection of either cocaine or saline and presented to a novel environment where behavior was recorded for 30 min. Adolescent females (PND 45) that were handled prior to cocaine administration demonstrated elevated levels of cocaine-induced activity relative to their age-matched non-handled counterparts and also to their handled-adult counterparts. In contrast, among non-handled animals, young adults (PND 60) exhibited elevated drug-induced locomotion at several time points during the trial. Non-handled adolescent animals demonstrated the previously described "hyporesponsive" behavioral profile relative to their non-handled adult counterparts. The results from the present experiment indicate that adolescent animals may be more sensitive to basic laboratory manipulations such as pre-test handling, and care must be taken when utilizing adolescent animals in behavioral testing. Handling appears to be a sensitive manipulation in elucidating differences in cocaine-induced behavioral activation between ages.

Age Factors↗

PubMed2005

Handling alters cocaine-induced activity in adolescent but not adult male rats.

The developmental period of adolescence is one that is characterized by increased levels of stress and vulnerability to drugs. Pre-test handling is an experimental manipulation that is used to acclimate animals prior to behavioral testing and exposure to a novel environment. Therefore, the present study was conducted in order to address the issue of pre-test handling of adolescent and adult male rats on subsequent cocaine-induced locomotor activity upon presentation to a novel environment. On days one through four, postnatal day (PND) 41-44 or PND 56-59, respectively, animals were handled b.i.d. for three minutes. On the fifth day, PND 45 or PND 60, animals were administered 30 mg/kg/ip cocaine or saline and immediately placed in a novel environment where locomotor activity was measured for 30 minutes. Cocaine increased locomotor activity similarly in all non-handled animals, regardless of age. Interestingly, adolescent animals expressed a differential effect when handled prior to an acute cocaine administration. Specifically, handling increased cocaine-induced locomotor activity in adolescent but not adult animals. These findings indicate that adolescent males that have been acclimated to the handling procedure experience significantly more behavioral reactivity than do adults to a high dose of cocaine upon exposure to a novel environment.

Age Factors↗

PubMed2005

Heightened cocaine-induced locomotor activity in adolescent compared to adult female rats.

Initiation and experimentation with illicit drugs often occurs in adolescence. Evidence suggests that adolescent rats are more sensitive to some of the effects of drugs of abuse than adult rats. The present study investigated whether adolescent and adult female Sprague Dawley rats differ in cocaine-induced locomotor activity. Animals were placed in the test environment for 30 minutes, and then administered an intraperitoneal (IP) injection of either cocaine (20mg/kg) or saline (0.9%). Both adult and adolescent animals showed significant increases in locomotor activity as a result of cocaine administration compared to saline controls. Interestingly, cocaine induced significantly more locomotor activity in the adolescent females compared to the adults, demonstrating that cocaine acts differently in developing animals.

Age Factors↗

PubMed2004

Developmental differences in nicotine place conditioning.

To understand the motivations and implications of the prevalence of smoking, studies have compared the behavioral effects of nicotine, the psychoactive drug in tobacco, in adolescent and adult animals. The present study used a biased three-chambered conditioned-place preference procedure without prior habituation to examine the potential rewarding and anxiolytic effects of nicotine across adolescence and adulthood to assess the presence of age-dependent differences in response to nicotine.

Age Factors↗

PubMed2004

An animal model of sensation seeking: the adolescent rat.

Previous research has established a strong relationship between a rodent's preference for novelty and sensitivity to psychomotor stimulants. Rats with greater sensitivity to the motoric effects of amphetamine exhibit higher preferences for novelty. Additionally, animals with high novelty preference scores are more easily drug conditioned and are more sensitive to, and can more accurately discriminate, amphetamine doses. Novelty preference in animals has been compared to sensation seeking in humans and is strongly correlated with drug use and addiction vulnerability. Thus, the present studies employed a playground maze procedure to measure changes in novelty preference across age following either four or eight habituation trials using eight distinct objects. Early-adult (postnatal day [PND] 59) animals did not exhibit a significant preference for a novel object regardless of total number of habituation trials. Early-adolescent animals (PND 34) exhibited a preference for the novel object in fewer than four habituation trials, but exhibited no preference with increased habituation trials. These results are counterintuitive and may demonstrate an overgeneralization of the habituation trials specific to adolescent animals. Given that adolescence is a period of heightened exploration, one would expect adolescent animals to demonstrate an enhanced preference for novel stimuli using this paradigm. However, it is possible that the complexity of the task, as presented, reveals differences in the establishment and behavioral manifestation of associations during adolescence. To address this issue, a separate novelty paradigm was implemented using an open-field habituation procedure followed by the introduction of a single novel object during the testing period. This revised design provides the foundation needed to better assess novelty-induced locomotor activity and novelty preference in adolescent rats.

Adolescent↗