Andrea
G. Gillman
Graduate Student/Research Assistant
Behavior Systems and Learning Lab
Department of Psychological & Brain Sciences
Indiana University Bloomington
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Address: 1101 E. 10th St Email: aggillma@indiana.edu I am currently in the third year of the Ph.D. program, majoring in Neuroscience and Psychology (Biology & Behavior specialization). My research examines circadian activity entrainment induced by addictive drugs. This page contains descriptions of some of the projects I am currently working on. Here's a link to my CV. |
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Research Projects:
First-Year Project: Pre– and post-nicotine circadian activity rhythms can be differentiated by a paired environmental cue. Physiology & Behavior, 93(1-2), 337-350.
Previous studies have shown that addictive drugs presented daily at fixed times produce circadian (oscillator-driven) anticipatory and evoked activity rhythms in rats. Other studies have shown that environmental cues paired with addictive drugs produce tolerance to drug effects and elicit craving behavior when presented without the drug. The present study tested these circadian entrainment and paired-cue conditioning effects together. This study compared the ability of daily nicotine and saline injections at different fixed times to entrain pre-injection (anticipatory) and post-injection (evoked) circadian activity rhythms in two groups of female Sprague-Dawley rats. One group (Paired) had an environmental cue (a tone) paired with the effects of the nicotine injection, and the second group (Unpaired) had the tone paired with the effects of the saline injection. The rats were housed singly for 56 days in chambers with attached wheels under constant dim light and rate-limited food access. During three separate injection phases, nicotine and saline were administered daily at different fixed times, and the tone was presented at the second injection time. Three multi-day test phases examined circadian activity (a) without injections or tone, (b) with the tone alone at normal and novel times, and (c) with the tone absent and with injections occurring at normal and novel times. The results showed that nicotine entrained both pre-and post-injection circadian oscillators, and the nicotine-paired tone interfered with pre-injection anticipatory activity.
[Pre- and post-nicotine circadian POSTER.pdf]
Second-Year Project: Nicotine administration produces robust entrainment of activity in both the absence and presence of food and light zeitgebers. [Manuscript in preparation]
Administration of addictive drugs, such as nicotine, on both 24 hour (circadian) and 31 hour (infradian) schedules has been shown to entrain circadian activity patterns that persist for at least 2 days when the drug is withheld. Most of the studies that have investigated this phenomenon have done so under constant lighting conditions and rate-limited feeding to negate the influences of the food- and light-entrainable circadian oscillators. This study compared wheel running, drinking, and feeding behaviors in female Sprague-Dawley rats under both rate-limited and ad libitum food schedules (Experiment 1), and under both constant and varying light schedules (Experiment 2). In all rats, activity became entrained to the nicotine administration time, and both pre-injection (anticipatory) and post-injection (elicited) activity patterns were observed for feeding, drinking, and wheel running. These activity patterns entrained to new administration times when the nicotine injections were moved to different times of the day. When injections were withheld on test days, nicotine-entrained activity persisted around the nicotine injection time for 2 to 4 days. No significant differences in activity levels were found between the two food availability schedules in Experiment 1. For the differing light schedules in Experiment 2, no significant differences were found for pre-injection activity. Post-injection activity persisted for a longer period of time under the fixed light schedule than under the varying light schedule. These results show that endogenous circadian activity patterns will entrain to nicotine administration times under both normal and novel zeitgeber conditions. These results also provide further evidence that the pre-injection and post-injection activity rhythms are controlled by separate oscillators.
[Nicotine circadian fixed & variable zeitgebers POSTER.pdf]
Ongoing NIDA-funded projects:
1. Fentanyl, but not haloperidol, entrains persistent circadian activity patterns when administered on 24-hour schedules. [Manuscript in preparation]
Fixed daily administration of addictive drugs has been shown to shift and entrain endogenous circadian activity rhythms. This study investigated the abilities of fentanyl, an opiate, and haloperidol, a non-addictive anti-psychotic, to entrain wheel running, drinking, and feeding activity under a 24-hour (circadian) injection schedule. For each drug, 24 female Sprague-Dawley rats were kept in chambers with attached wheels for 94 days under constant dim light and rate-limited feeding. Subjects were divided into 3 groups of 8 rats, each receiving a different dosage. Following a 22-day acclimation period, fentanyl or haloperidol was administered i.p. every 24 hours for three 8-day injection series, each followed by a 3-day test phase where injections were withheld. For fentanyl, wheel running, drinking, and feeding entrained to the drug administration time in all dosage groups. Pre-injection anticipatory activity was evident 1-2 hours prior to the daily administration time. Post-injection activity lasted for approximately 6 hours, with 3 hours of elevated activity followed by 3 hours of reduced activity. When injections were withheld during the test periods, fentanyl-entrained activity rhythms persisted around the injection time for 2-3 days. In contrast to the fentanyl results, haloperidol did not entrain any of the recorded activity measures. After each haloperidol injection, an elicited activity decline persisted for approximately 10-12 hours. However, there was no evidence of a consistent pre-injection anticipation, and although the free-running rhythms were interrupted by haloperidol-induced sedation, entrainment to the haloperidol injection time was not evident. These results show that fentanyl, but not haloperidol, can entrain circadian activity rhythms that persist at the previous administration time for multiple days after injections cease.
2. Fentanyl, but not haloperidol, produces circadian post-administration ensuing activity patterns when administered on 31-hour schedules. [Manuscript in preparation]
3. Nicotine and ethanol entrain persistent circadian activity patterns when administered on a 24-hour schedule. [Manuscript in preparation]
4. Nicotine and ethanol produce circadian post-injection ensuing activity patterns when administered on 31-hour schedules. [Manuscript in preparation]
[NIDA screening studies POSTER.pdf]
5. Entrainment of circadian
activity rhythms by multiple daily nicotine administrations.
(Special thanks to Lauren Harold, my summer research assistant, for putting
together this poster!)
[Nicotine multiple daily administrations POSTER.pdf]
Dissertation Projects: Drug-entrained circadian rhythms as a novel target for addiction treatment.
There is increasing evidence that circadian entrainment of behavioral and/or physiological processes may play a role in drug addiction and its related behaviors. When rats are given daily injections of addictive drugs such as methamphetamine, nicotine, or alcohol, they develop locomotor activity rhythms that precede the injection time, and these rhythms will persist and oscillate on a 24-hr interval for several days when the drug is withheld. These drug-entrained activity rhythms may contribute to craving and drug-seeking behaviors, and may also relate to withdrawal effects and relapse. If circadian entrainment is indeed a component of drug addiction, a behavioral or pharmacological treatment that could block or disrupt these rhythms could potentially be more effective than one without this ability. The proposed research will focus specifically on nicotine, a widely-used and highly addictive psychomotor stimulant. Nicotine injections will be administered every 24 hours for 16 days, which in previous studies has produced robust entrainment. Upon completion of this injection series, a selected treatment will be administered for 2 days at the administration time in place of the nicotine injection. Following this treatment series, the rats will be left undisturbed for 4 days so that persisting activity oscillations may be observed. A second 8-day nicotine injection series will be performed with a subsequent treatment period to observe any alterations in activity during nicotine reinstatement. The proposed research will compare the abilities of three types of treatments to disrupt nicotine-entrained activity rhythms. The first type of treatment targets associative learning processes (cue extinction). The second targets the specific pharmacological effects of nicotine (mecamylamine, bupropion). Finally, two pharmacological treatments will be tested that have been shown to disrupt circadian patterns of sleep (Ro 15-4513) and food intake (SB-334867). In this experimental paradigm, an ideal treatment would directly suppress the activity bouts entrained to the nicotine injection time on the treatment days and also eliminate any persisting activity bouts on the subsequent 2 days, which would indicate a successful disruption of circadian entrainment.
More to come!
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