Article

Intravenous ethanol/cocaine self-administration initiates high intake of intravenous ethanol alone

Division of Pharmacology & Toxicology, University of Texas at Austin, Austin, Texas, United States
Pharmacology Biochemistry and Behavior (Impact Factor: 2.78). 08/2002; 72(4):787-94. DOI: 10.1016/S0091-3057(02)00738-4
Source: PubMed

ABSTRACT

Evidence suggests that ethanol (EtOH) preexposure influences the rewarding valence of subsequent EtOH use. This study was conducted to determine if EtOH preexposure through EtOH/cocaine self-administration facilitates the motivational effects of EtOH alone. Rats self-administered intravenous (iv) EtOH/cocaine combinations (EtOH/Cocaine Fading group; EtOH 125.0 mg/kg/inj+Cocaine 0.1-0.75 mg/kg/inj) during a preexposure period. Consequently, these rats self-administered intravenous EtOH alone (62.5, 125.0, 250.0 and 500.0 mg/kg/inj) significantly more than a control group with prior cocaine self-administration experience (0.1-0.75 mg/kg/inj). In addition, at equal EtOH intake levels, locomotor activity was significantly enhanced in the EtOH/Cocaine Fading group but not the Cocaine Control animals (P=.01). The amount of EtOH self-administered in the EtOH/Cocaine Fading group during 1-h sessions (approximately 0.5-2.0 g/kg) corresponded with blood alcohol levels (BAL) ranging from 44 to 221 mg/dl. The highest BALs reported here have not previously been demonstrated after voluntary EtOH intake through any route of administration. These data suggest that preexposure to EtOH during EtOH/cocaine self-administration sessions modified neural substrates underlying both the reinforcing and locomotor responses to EtOH alone. Further studies utilizing intravenous EtOH self-administration will allow identification of various long-term behavioral and neural consequences of voluntary high EtOH intake.

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    • "Such experimenter-controlled manipulations allow for neither the examination of the underlying motivation to consume high levels of alcohol nor the neurological underpinnings of human alcohol addiction. Escalated IV ethanol selfadministration has also been demonstrated when rats have either previous or concurrent exposure to other drugs of abuse, such as cocaine (Ikegami et al., 2002) or heroin (Hyytiä, Schulteis, & Koob, 1996). However, such studies similarly fail to answer questions relevant to human alcohol abuse. "
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    ABSTRACT: Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally “relevant” effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding “non-pharmacological” effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol’s effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol self-administration methodology cannot overcome the aversive properties of ethanol via this route in the rat.
    Full-text · Article · Aug 2014 · Alcohol
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    • "Thus, the chronic absence of the stress component during intravenous injections may lead to different long-term physiological effects compared to the intraperitoneal route of administration. Though significantly greater than previous studies of intravenous EtOH administration (Hyytia et al., 1996; Kuzmin et al., 1999), EtOH self-administration in EtOH + SKF81297 pretreated groups in the present report was not as robust as our prior report when animals self-administered EtOH + cocaine prior to EtOH-reinforced sessions (Ikegami et al., 2002). An obvious difference in these studies is that, through enhanced extracellular concentrations of DA, cocaine administration results in stimulation of all available DA receptors, while SKF81297 is a specific agonist of the D1 receptor. "
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    ABSTRACT: Separate lines of evidence suggest that neuroadaptations associated with ethanol (EtOH) reinforcement can be initiated by chronic EtOH preexposure and a signaling pathway activated by dopamine (DA) D1 receptor stimulation. We have previously shown that rewarding and locomotor effects of EtOH alone [Pharmacol. Biochem. Behav. 72 (2002) 787] are enhanced after chronic exposure to self-administered EtOH/cocaine combinations. To determine the importance of chronic EtOH exposure, dopamine D1 receptor activation and mode of drug administration in EtOH reward, animals were given daily intravenous infusions of experimenter-administered saline, EtOH (2.0 g/kg), the DA D1 receptor agonist, SKF81297 (0.2 mg/kg), or EtOH+SKF81297 over a 4-week period. Compared to other groups, animals preexposed to EtOH+SKF81297 self-administered significantly greater amounts of intravenous EtOH and showed greater enhancement and less suppression of locomotor activity in response to a range of intravenous EtOH dosages (0.125, 0.25, 0.5, 1.0 and 1.5 g/kg). Since chronic treatment with EtOH alone did not enhance EtOH-induced reinforcement or locomotor activity, it is unlikely that these effects were due to EtOH tolerance. These findings suggest that chronic D1 receptor activation combined with EtOH administration alters neural responsiveness to EtOH and support the notion that D1 activation is important to EtOH reward.
    Full-text · Article · Oct 2003 · Pharmacology Biochemistry and Behavior
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    • "Thus, the chronic absence of the stress component during intravenous injections may lead to different long-term physiological effects compared to the intraperitoneal route of administration. Though significantly greater than previous studies of intravenous EtOH administration (Hyytia et al., 1996; Kuzmin et al., 1999), EtOH self-administration in EtOH + SKF81297 pretreated groups in the present report was not as robust as our prior report when animals self-administered EtOH + cocaine prior to EtOH-reinforced sessions (Ikegami et al., 2002). An obvious difference in these studies is that, through enhanced extracellular concentrations of DA, cocaine administration results in stimulation of all available DA receptors, while SKF81297 is a specific agonist of the D1 receptor. "

    Full-text · Article · Sep 2003 · Pharmacology Biochemistry and Behavior
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