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Articles by Esther Y. Maier in JoVE
JoVE Neuroscience
अल्ट्रासोनिक vocalizations चूहे में स्व - प्रशासन औषधि के दौरान मूल्यांकन
1College of Pharmacy, Division of Pharmacology and Toxicology, University of Texas at Austin, 2The Waggoner Center of Addiction and Alcohol Research, University of Texas at Austin, 3Department of Psychology, University of Michigan, 4Institute for Neuroscience, University of Texas at Austin, 5Department of Psychology, University of Texas at Austin
स्वयं प्रशासन और अल्ट्रासोनिक vocalizations औषधि (USV) पशु अनुसंधान में व्यवहार आकलन के रूप में उपयोग किया जाता है, लेकिन शायद ही कभी संयोजन में. इस अनुच्छेद के प्रयोजन के लिए स्वयं दवा प्रशासन की प्रक्रिया के दौरान रिकॉर्डिंग USVs के लाभ दवा अनुभव करने के लिए उत्तेजित प्रतिक्रियाओं का आकलन का वर्णन है.
Other articles by Esther Y. Maier on PubMed
Experience-dependent Changes in Temperature and Behavioral Activity Induced by MDMA
Hyperthermia and hyperlocomotor activity are commonly reported acute effects of high dose, experimenter-delivered 3,4-methylenedioxymethamphetamine (MDMA). The current investigation was performed to determine short- to long-term physiological and behavioral changes induced by moderate intake MDMA self-administration. In the present study, rats self-administered MDMA (approx. 2.0-7.0 mg/kg/day) across 20 days during daily 2-h operant sessions. Locomotor activity was assessed during MDMA self-administration sessions and core temperatures were recorded before and after each session. Findings of the first several sessions showed core temperatures significantly decreased after MDMA self-administration compared to baseline and to a control group that self-administered saline during operant sessions. As sessions proceeded, the MDMA-induced hypothermic response diminished and core temperatures normalized, then increased during the last few sessions. Also, locomotor activity during MDMA self-administration sessions was initially equivalent to saline level activity, but increased by day 8 to significantly greater levels. Our findings demonstrate experience-dependent changes after voluntary administration of MDMA that are clearly observable in temperature regulation and behavioral activity.
Diazepam Alters Cocaine Self-administration, but Not Cocaine-stimulated Locomotion or Nucleus Accumbens Dopamine
Cocaine is known to enhance nucleus accumbens dopamine (NAcc DA), to serve as a positive reinforcer and to produce negative effects, such as anxiety. The influence of diazepam on cocaine intake, cocaine-stimulated behavioral activity and NAcc DA was investigated using self-administration and experimenter-administered intravenous (i.v.) cocaine. In Experiment 1, rats were pretreated with diazepam (0.25 mg/kg) or saline (0.1 ml) 30 min prior to 20 daily 1-hour cocaine (0.75 mg/kg/injection) self-administration sessions. Cocaine intake increased for all animals across sessions, but was highest in diazepam-pretreated animals. Diazepam rats also self-administered their first cocaine injection of each session faster than controls. Experiment 2 utilized in vivo microdialysis to assess NAcc DA levels before and after experimenter-administered i.v. cocaine injections (0.75 mg/kg/injection x 2; 10-min interval) in diazepam- and saline-pretreated rats. Group differences were not revealed across basal and cocaine-stimulated NAcc DA assessments, indicating that diazepam did not decrease NAcc DA during cocaine self-administration. Findings that diazepam enhances cocaine self-administration and decreases cocaine response latency support the notion that cocaine-induced anxiety limits voluntary cocaine intake. It is further suggested that individual variations in cocaine-induced aversive effects may determine whether cocaine use is avoided or repeated.
Repeated Intravenous Amphetamine Exposure: Rapid and Persistent Sensitization of 50-kHz Ultrasonic Trill Calls in Rats
Short 50-kilohertz (kHz) range frequency-modulated ultrasonic vocalizations (USVs) produced by rats and mice are unconditionally elicited by drugs of abuse or electrical stimulation that increase dopamine activity in the nucleus accumbens, and it has been suggested that they reflect "positive affect" or incentive motivational states associated with appetitive behavior. The repeated administration of amphetamine is known to not only produce "psychomotor" sensitization, but also to facilitate a number of appetitive behaviors, including conditioned drug pursuit behavior. We were interested, therefore, in whether amphetamine-induced 50-kHz USVs would also increase with repeated drug exposure. USV recordings were made during 5-min sessions immediately after a saline infusion, and again 4-5h later after 1.0mg/kg intravenous amphetamine exposure. These sessions took place every other day over a 5-day period. A challenge dose of 1.0mg/kg amphetamine was administered 2 weeks later to determine whether sensitization would persist. The initial amphetamine infusion increased 50-kHz USVs relative to the saline infusion. This effect was enhanced over trials and during the amphetamine challenge 2 weeks later. Classification of 50-kHz range call types revealed that complex frequency-modulated trill calls were sensitized by amphetamine, but not flat 50-kHz calls. It is possible that 50-kHz USV recordings could provide a potentially valuable behavioral measure of sensitization linked to enhanced incentive salience and increased tendency to self-administer drugs of abuse.
Behavioral, Thermal and Neurochemical Effects of Acute and Chronic 3,4-methylenedioxymethamphetamine ("Ecstasy") Self-administration
3,4-Methylenedioxymethamphetamine (MDMA) is a popular methamphetamine derivative associated with young adults and all-night dance parties. However, the enduring effects of MDMA at voluntary intake levels have not been extensively investigated. In this study, MDMA-influenced behaviors and core temperatures were assessed over the course of 20 daily MDMA self-administration sessions in rats. In vivo microdialysis techniques were used in a subsequent MDMA challenge test session to determine extracellular nucleus accumbens dopamine (NAcc DA) and serotonin (5-HT) levels in MDMA-experienced and naïve animals before and after a self-administered MDMA injection (3.0mg/kg, i.v.). During self-administration sessions, gradual and significant increases in MDMA intake and MDMA-stimulated locomotor activity were observed across sessions. Core temperature significantly decreased during initial MDMA sessions, but was unaltered by the last 10 sessions. In the MDMA challenge test, MDMA-naïve rats showed significantly higher NAcc 5-HT responses compared to MDMA-experienced rats, though MDMA experience did not affect the magnitude of NAcc DA response. The overall findings suggest that changes in MDMA-induced responses over the course of increasing levels of drug exposure may reflect the development of tolerance to a number of MDMA effects.
Repeated Intravenous Cocaine Experience: Development and Escalation of Pre-drug Anticipatory 50-kHz Ultrasonic Vocalizations in Rats
Ultrasonic vocalization (USV) in the 50-kHz range occurs in rats immediately upon first-time exposure to cocaine or amphetamine, and rapidly increases with repetitive drug exposure at the same dose. This sensitized positive-affect response to these drugs of abuse is persistent in that the peak level of USVs again appears when the drug is reintroduced after several weeks of drug discontinuation. The present study explored whether with enough experience USVs might be elicited, and gradually escalate, in anticipation of impending drug delivery. Rats were trained to self-administer (SA) cocaine intravenously by lever pressing 5 days per week for 4 weeks. Yoked rats received experimenter-delivered cocaine matching that of SA rats. USVs and locomotor activity were recorded during each 10-min period prior to 60-min drug access sessions. Extinction trials in which drug access was denied were then carried out over an additional 4-week period. After about a week of cocaine experience, both the SA and yoked groups began to progressively increase USVs when placed in an environment that predicted forthcoming drug exposure. Extinction of anticipatory calls and locomotion occurred over days after drug access ended. USVs may be a useful model for specifically investigating the neural basis of drug anticipation and aid in developing and assessing new addiction treatment strategies for reducing craving and relapse.
Cocaine Deprivation Effect: Cue Abstinence over Weekends Boosts Anticipatory 50-kHz Ultrasonic Vocalizations in Rats
In drug dependence studies, rats are often tested daily with short breaks (such as weekends) spent untested in their home cages. Research on alcohol models has suggested that breaks from continuous testing can transiently enhance self-administration (termed the "alcohol deprivation effect"). The present study explored whether the salience of cocaine-access cues is increased after skipping weekend cocaine and cue exposures. Ultrasonic vocalizations (USVs) of the 50-kHz class are emitted by rats exposed to intravenous cocaine and have been shown to increase with repeated drug exposure at the same dose level (sensitization). The present study found that over the course of several weeks of cocaine self- or yoked-administration pre-drug cues signaling forthcoming access or delivery of cocaine elicited marked amounts of anticipatory 50-kHz USVs, and that weekend deprivation from cues and cocaine exaggerated further the level of calling (more calls on Mondays compared to Fridays). Anticipatory USVs extinguished less rapidly when weekend access to unreinforced cues was denied. The results may have clinical implications, in that intermittently avoiding cues or context may enhance drug cue salience and resistance to extinction.
The Missing Variable: Ultrasonic Vocalizations Reveal Hidden Sensitization and Tolerance-like Effects During Long-term Cocaine Administration
Subtypes of 50-kHz ultrasonic vocalizations (USVs) in rats are thought to reflect positive affect and occur with cocaine or amphetamine delivery. In contexts predicting forthcoming cocaine, pre-drug anticipatory USVs are initially minimal during daily sessions but gradually escalate over several weeks, presumably as the animal learns to expect and look forward to impending drug access. To gain more insight into motivational aspects of cocaine intake in animal models of drug dependence studies, it is important to compare experience-dependent changes in lever response rate, USVs, and locomotion during cocaine conditioning and extinction trials.
