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Browsing by Subject "Pavlovian Spontaneous Recovery"
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Item Cocaine influences alcohol-seeking behavior and relapse drinking in alcohol-preferring (P) rats(Wiley Online Library, 2014-10) Hauser, Sheketha R.; Wilden, Jessica A.; Deehan Jr., Gerald A.; McBride, William J.; Rodd, Zachary A.; Department of Psychiatry, IU School of MedicineBACKGROUND: The results of several studies suggest that there may be common neurocircuits regulating drug-seeking behaviors. Common biological pathways regulating drug-seeking would explain the phenomenon that seeking for 1 drug can be enhanced by exposure to another drug of abuse. The objective of this study was to assess the time course effects of acute cocaine administration on ethanol (EtOH) seeking and relapse. METHODS: Alcohol-preferring (P) rats were allowed to self-administer 15% EtOH and water. EtOH-seeking was assessed through the use of the Pavlovian spontaneous recovery (PSR) model, while EtOH-relapse drinking was assessed through the use of the alcohol-deprivation effect. RESULTS: Cocaine (0, 1, or 10 mg/kg), injected immediately, 30 minutes, or 4 hours prior to the first PSR testing session, dose-dependently increased responding on the EtOH lever compared to extinction responses and responding by saline controls. Under relapse conditions, cocaine given immediately prior to the relapse session had no effect (1 mg/kg) or reduced responding (10 mg/kg). In contrast, cocaine given 4 hours prior to the relapse session markedly enhanced EtOH responding compared to saline. CONCLUSIONS: The enhanced expression of EtOH-seeking and EtOH-relapse behaviors may be a result of a priming effect of cocaine on neuronal circuits mediating these behaviors. The effect of cocaine on EtOH-relapse drinking is indicative of the complex interactions that can occur between drugs of abuse; production of conflicting behaviors (immediate), and priming of relapse/seeking (4-hour delay).Item Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats(Elsevier B.V., 2012-02) Dhaher, Ronnie; Toalston, Jamie E.; Hauser, Sheketha R.; Bell, Richard L.; McKinzie, David L.; McBride, William J.; Rodd, Zachary A.; Department of Psychiatry, IU School of MedicineResearch indicates opioid antagonists can reduce alcohol drinking in rodents. However, tests examining the effects of opioid antagonists on ethanol seeking and relapse behavior have been limited. The present study examined the effects of two opioid antagonists on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Adult P rats were self-trained in two-lever operant chambers to self-administer 15% (vol/vol) ethanol on a fixed-ratio 5 (FR5) versus water on a FR1 concurrent schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent extinction training, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without ethanol or water to measure responses on the ethanol and water levers for four sessions. After a subsequent 2 weeks in the home cage, without access to ethanol, rats were returned to the operant chambers with ethanol and water available. Effects of antagonists on maintenance responding were tested after several weeks of daily 1-h sessions. Naltrexone (NAL; 1–10 mg/kg, subcutaneously [s.c.]; n = 8/dose), LY255582 (LY; 0.03–1 mg/kg, s.c.; n = 8/dose), or vehicle were injected 30 min before the first session (in the absence of ethanol), following 2 weeks in their home cages, and for four consecutive sessions of ethanol self-administration under maintenance and relapse conditions. Both NAL and LY reduced responses on the ethanol lever without any fluids present, and ethanol self-administration under relapse and on-going drinking conditions, with LY being more potent than NAL. Both NAL and LY were less effective in reducing responding in the absence of ethanol than in reducing ethanol self-administration. Overall, the results indicate that the opioid system is involved in mediating ethanol seeking, and ethanol self-administration under relapse and on-going alcohol drinking, but that different neurocircuits may underlie these behaviors.Item Enhanced alcohol-seeking behavior by nicotine in the posterior ventral tegmental area of female alcohol-preferring (P) rats: modulation by serotonin-3 and nicotinic cholinergic receptors(Springer, 2014-09) Hauser, Sheketha R.; Deehan Jr., Gerald A.; Toalston, Jamie E.; Bell, Richard L.; McBride, William J.; Rodd, Zachary A.; Psychiatry, School of MedicineRATIONALE: Alcohol and nicotine co-use can reciprocally promote self-administration and drug-craving/drug-seeking behaviors. To date, the neurocircuitry in which nicotine influences ethanol (EtOH) seeking has not been elucidated. Clinical and preclinical research has suggested that the activation of the mesolimbic dopamine system is involved in the promotion of drug seeking. Alcohol, nicotine, and serotonin-3 (5-HT3) receptors interact within the posterior ventral tegmental area (pVTA) to regulate drug reward. Recently, our laboratory has reported that systemic administration of nicotine can promote context-induced EtOH seeking. OBJECTIVES: The goals of the current study were to (1) determine if microinjections of pharmacologically relevant levels of nicotine into the pVTA would enhance EtOH seeking, (2) determine if coadministration of nicotinic cholinergic receptor antagonist (nACh) or 5-HT3 receptor antagonists would block the ability of nicotine microinjected into the pVTA to promote EtOH seeking, and (3) determine if 5-HT3 receptors in the pVTA can modulate EtOH seeking. RESULTS: Nicotine (100 and 200 μM) microinjected into the pVTA enhanced EtOH seeking. Coinfusion with 200 μM mecamylamine (nACh antagonist) or 100 and 200 μM zacopride (5-HT3 receptor antagonist) blocked the observed nicotine enhancement of EtOH seeking. The data also indicated that microinjection of 1 μM CPBG (5-HT3 receptor agonist) promotes context-induced EtOH seeking; conversely, microinjection of 100 and 200 μM zacopride alone reduced context-induced EtOH seeking. CONCLUSIONS: Overall, the results show that nicotine-enhanced EtOH-seeking behavior is modulated by 5-HT3 and nACh receptors within the pVTA and that the 5-HT3 receptor system within pVTA may be a potential pharmacological target to inhibit EtOH-seeking behaviors.Item Nicotine Modulates Alcohol-Seeking and Relapse by Alcohol-Preferring (P) Rats in a Time Dependent Manner(Wiley, 2012-01) Hauser, Sheketha R.; Getachew, Bruk; Oster, Scott M.; Dhaher, Ronnie; Ding, Zheng-Ming; Bell, Richard L.; McBride, William J.; Rodd, Zachary A.; Department of Psychiatry, IU School of MedicineBackground— Alcohol is frequently co-abused with smoking. In humans, nicotine use can increase alcohol craving and consumption. The objectives of the current study were to assess the acute effects of nicotine on alcohol seeking and relapse at two different time points. Method— Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5 – fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hr sessions. Following 10 weeks of daily 1-hr sessions, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without EtOH or water being present for 4 sessions (Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0, 0.1, 0.3, or 1.0 mg/kg) was injected s.c. immediately or 4-hr prior to PSR or relapse testing. Results— Injections of nicotine immediately prior to testing reduced (5–10 responses PSR; 50– 60 responses relapse), whereas injections of nicotine 4-hr prior to testing increased (up to 150 responses for PSR; up to 400 responses for relapse with 1.0 mg/kg dose) responses on the EtOH lever during PSR and relapse tests. Discussion— The results of this study demonstrate that acute effects of nicotine on EtOH- seeking and relapse behaviors may be time-dependent, with the immediate effects being a result of nicotine possibly acting as a substitute for EtOH whereas, with a delay of 4-hr, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine’s metabolites (i.e., cotinine, nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors.Item Oral Conditioned Cues Can Enhance or Inhibit Ethanol (EtOH)-Seeking and EtOH-Relapse Drinking by Alcohol-Preferring (P) Rats(Wiley, 2016-04) Knight, Christopher P.; Hauser, Sheketha R.; Deehan, Gerald A.; Toalston, Jamie E.; McBride, William J.; Rodd, Zachary A.; Psychiatry, School of MedicineBACKGROUND: Conditioned cues can elicit drug-seeking in both humans and rodents. The majority of preclinical research has employed excitatory conditioned cues (stimuli present throughout the availability of a reinforcer), but oral consumption of alcohol is similar to a conditional stimuli (presence of stimuli is paired with the delivery of the reinforcer) approach. The current experiments attempted to determine the effects of conditional stimuli (both excitatory and inhibitory) on the expression of context-induced ethanol (EtOH)-seeking. METHODS: Alcohol-preferring (P) rats self-administered EtOH and water in standard 2-lever operant chambers. A flavor was added to the EtOH solution (CS+) during the EtOH self-administration sessions. After 10 weeks, rats underwent extinction training (7 sessions), followed by a 2-week home cage period. Another flavor was present during extinction (CS-). Rats were exposed to a third flavor in a non-drug-paired environment (CS(0)). EtOH-seeking was assessed in the presence of no cue, CS+, CS-, or CS(0) in the dipper previously associated with EtOH self-administration (no EtOH available). Rats were maintained a week in their home cage before being returned to the operant chambers with access to EtOH (flavored with no cue, CS+, CS-, or CS(0)). RESULTS: The results indicated that the presence of the CS+ enhanced EtOH-seeking, while the presence of the CS- suppressed EtOH-seeking. Similarly, adding the CS- flavor to 15% EtOH reduced responding for EtOH while the CS+ enhanced responding for EtOH during relapse testing. CONCLUSIONS: Overall, the data indicate that conditional stimuli are effective at altering both EtOH-seeking behavior and EtOH-relapse drinking.