Browsing by Subject "Self-administration"
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Item Acquisition of cocaine and heroin self-administration in rats developmentally exposed to lead(Texas A&M University, 2005-08-29) Rocha, AngelicaRationale: The rate of acquisition of drug self-administration may serve as a predictor of later drug-taking behavior, possibly influencing vulnerability to initiate drug use. Objectives: The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous (i.v.) heroin self-administration and cocaine self-administration using an automated procedure that included both Pavlovian and operant components. Methods: For Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Metal administration continued through pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21). Animals born to control or lead-exposed dams received indwelling jugular catheters as adults and subsequently were tested daily in a preparation where sessions included an initial 3-hr autoshaping period followed by a 3- hr self-administration period. During autoshaping, heroin (.018 mg/kg) infusions were paired with the extension and retraction of a lever when a lever press was not made for 15 sec, while infusions occurred during self-administration only when a lever press was executed (FR-1). The criterion for acquisition was a 2-day period during which a mean of 10 infusions/session occurred during self-administration. Animals were given 35 days to reach criterion. Results: Findings from Experiment 1 showed the proportion of rats meeting the lever-press response criterion for heroin when tested as adults was lower among lead-exposed animals. In Experiment 2, cocaine (.20 mg/kg) was presented to animals that underwent the same metal-exposure regimen, surgical procedures and methods with variations only in the number of infusions that were automatically administered during the Pavlovian component. Criterion for cocaine acquisition was a mean of 50 infusions over a two-day. In Experiment 2, a greater proportion of leadexposed animals reached the criterion for cocaine acquisition. Conclusions: Developmentally lead-exposed animals showed a decrease in vulnerability to initiate drug-taking behavior when presented with heroin in the adult phase, relative to controls. In contrast, developmentally lead-exposed animals showed an enhanced vulnerability to reach the criterion for cocaine self-administration. Clinical relevance of developmental exposure to lead and the attendant vulnerability to self-administer drugs of abuse is discussed.Item Affective responses in cocaine-experienced rats reveal cue-induced drug craving and cocaine reward magnitude(2011-08) Maier, Esther Yvonne; Duvauchelle, Christine L.; Schallert, Timothy; Gonzales, Rueben A.; Gore, Andrea C.; Monfils, Marie H.The development and persistence of cocaine dependence are greatly influenced by emotional affect and cocaine associative learning. Cocaine is known to enhance nucleus accumbens (NAcc) dopamine, serve as a positive reinforcer and produce negative effects, such as anxiety that may influence cocaine intake behavior. In the first study, I investigated the effects of the anxiolytic, diazepam on NAcc dopamine levels and cocaine self-administration behavior. These are two factors associated with cocaine rewarding effects. Diazepam has no effect on NAcc dopamine, but affects cocaine self-administration. This supports the notion that decreasing the anxiogenic effects of cocaine increases the rewarding value in a dopamine independent manner. Therefore, increasing the aversive effects of cocaine might be a novel approach to fight cocaine dependence. In the second study, I studied cocaine-induced associative learning and changes in affect during cocaine conditioning and extinction. 50-kHz ultrasonic vocalizations (USVs) in rats are thought to reflect positive affect and occur upon appetitive stimuli and with cocaine delivery. First, I explored whether USVs might be elicited in anticipation of impending drug delivery. Shortly into conditioning, rats elicited USVs when placed in the cocaine-associated environment. USVs progressively increased, indicating a growing learned association between cocaine intake and cocaine-associated cues. This suggests that USVs may be a useful model for investigating cocaine craving and serve as a pharmacological target for interventions aimed to reduce cocaine craving and relapse. I then examined the effects of short-term deprivation of cocaine and cocaine cues on cocaine-conditioned USVs, which were both exaggerated after abstinence. The results may have clinical implications, in that intermittently avoiding cues or context may enhance drug cue salience and increase the probability of relapse. Motivational aspects of cocaine were assessed comparing commonly measured lever response rate and locomotion with cocaine-induced USVs during cocaine administration and extinction. In agreement with prevailing findings, lever responding for cocaine and cocaine-induced locomotor activity increased across conditioning sessions. However, the number of USVs evoked in response to cocaine infusion decreased with cocaine experience. These findings suggest growing tolerance to the rewarding properties of cocaine. These studies underscore the value of USV assessment during drug dependence studies.Item Ethanol priming and its effects on consumption and accumbal plasticity(2015-12) Meyers, Tira Anne; Morrisett, Richard A.; Duvauchelle, Christine LAlcohol abuse and dependence are major concerns in the United States because of their chronic, detrimental health effects and societal costs. The mesocorticolimbic pathway and the nucleus accumbens (NAc), in particular, play critical roles in the formation of drug dependence and expression of drug related behaviors. The NAc contains two subregions, the core and shell, which encode different aspects of drug responding and have distinct dopamine responses. The accumbens can be further divided into two subpopulations of D1-dopamine receptor (D1) or D2-dopamine receptor (D2) expressing medium spiny neurons (MSNs) that precipitate different intracellular cascades and actions upon the reward circuitry. Alterations in the expression N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the D1 MSNs of the NAc shell are seen following chronic intermittent ethanol (CIE) exposure and sustained operant responding. To our knowledge, however, LTD induction has not been extensively studied in volitional self-administration. Prior to operant training, pre-exposure of ethanol, or ethanol priming, is necessary to develop the association of the positive effects of ethanol, but it has not been shown if similar changes in LTD induction occur during this brief ethanol exposure. The purpose of this thesis is to review the current research studying alcohol and its effects on accumbal plasticity, a preview of my work depicting an ethanol-only operant self-administration protocol, and the future directions of alcohol research.Item The pharmacological effects of acute ethanol on catecholamines in the medial prefrontal cortex and dorsal striatum(2016-12) Vena, Ashley; Gonzales, Rueben Anthony; Dominguez, Juan; Harris, Adron; Duvauchelle, Christine; Morrisett, RichardThe dorsal striatum and the medial prefrontal cortex are part of a neurocircuitry that is affected by acute and chronic drug use. In the present studies, we sought to characterize the pharmacological effects of ethanol on extracellular catecholamine concentrations in the dorsal striatum and medial prefrontal cortex. To this end, we utilized two different routes of administration to quantify ethanol’s actions. We performed in vivo microdialysis in adult, male Long Evans rats as they received single or repeated intravenous infusions of ethanol. Following infusion of a 1-g/kg dose of ethanol, we observed no significant effects on extracellular dopamine in either the dorsomedial or dorsolateral striatum, but in a separate group of animals, we observed significant stimulation of extracellular norepinephrine in the medial prefrontal cortex. However, following a cumulative intravenous dosing protocol, we observed a gradual ramping up of tonic dopamine activity in the dorsal striatal subregions, which was more robust in the dorsomedial striatum. Subsequently, we performed in vivo microdialysis in separate groups of rats during an operant self-administration session to quantify the time course of extracellular dopamine and norepinephrine in the medial prefrontal cortex. In the seven operant sessions prior to the microdialysis test session, each group of rats had been assigned to a separate treatment group: one that received a sweetened ethanol solution, one that received a sucrose solution, and a handling control group that did not receive any drinking solutions. In the ethanol-experienced animals, we report a reduction in basal dopamine and norepinephrine in the medial prefrontal cortex, relative to control groups. However, there were no significant differences in the temporal profile of extracellular norepinephrine across the three treatment groups. These studies demonstrate that limited voluntary ethanol consumption appears to be sufficient to alter tonic catecholamine signaling in the medial prefrontal cortex. Additionally, we conclude that central catecholamine signaling pathways are a target for ethanol.