Operant Self-administration (operant + self-administration)

Distribution by Scientific Domains


Selected Abstracts


Operant Self-Administration of Ethanol in Sardinian Alcohol-Preferring Rats

ALCOHOLISM, Issue 11 2002
Giovanni Vacca
Background "Work" for ethanol, that is, the ability of a laboratory animal to press a lever to gain access to ethanol, has been proposed as (a) a requirement for definition of an animal model of alcoholism and (b) a measure of ethanol-reinforcing properties. The present study evaluated oral self-administration of ethanol under an operant (lever pressing) procedure in selectively bred Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. Methods Rats from both lines were initiated to self-administer 10% ethanol, on a fixed ratio 1 schedule and in daily 30 min sessions, by using the Samson sucrose fading procedure. Subsequently, rats were exposed to increasing concentrations of ethanol up to 30% on a fixed ratio 4 schedule. Finally, the extinction responding for ethanol, defined as the maximal number of lever responses reached by each rat in the absence of ethanol reinforcement, was determined. Results The results indicated that sP rats acquired and maintained lever pressing for ethanol, self-administering mean amounts of ethanol in the range of 0.6 to 1.1 g/kg/session, which gave rise to mean blood ethanol levels in the 30 to 45 mg% range. Extinction responding for ethanol in sP rats averaged 73. In contrast, once sucrose was faded out, sNP rats displayed minimal levels of responding for ethanol, and extinction responding averaged 6. Conclusions The results of the present study extend to the sP/sNP rat lines the finding that ethanol can be established as a reinforcer in selectively bred alcohol-preferring rats, whereas it has modest, if any, reinforcing properties in alcohol-nonpreferring rats. [source]


Increased Consumption but Not Operant Self-administration of Ethanol in Mice Lacking the RII, Subunit of Protein Kinase A

ALCOHOLISM, Issue 5 2006
Frank M. Ferraro III
Background: Accumulating evidence indicates that adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is involved in the neurobiological responses to ethanol. Previous reports indicate that mice lacking the RII, subunit of PKA (RII,,/,) voluntarily consume more ethanol than wild-type controls (RII,+/+) using 2-bottle testing procedures. Although such procedures primarily measure consummatory behavior, operant self-administration procedures allow analysis of consummatory as well as appetitive or "ethanol-seeking" behavior (i.e., lever pressing is required to gain access to the ethanol solution). Therefore, we determined whether the high ethanol consumption characteristic of RII,,/, mice would be complemented by increased appetitive ethanol-seeking behavior in an operant paradigm. Methods: RII,,/, (n=8) and RII,+/+ (n=8) mice were initially sucrose-faded until they were lever responding for nonsweetened ethanol (10, 14, and 18%). Following the self-administration testing, RII,+/+ and RII,,/, mice were given access to 2 bottles, one containing water and the other ethanol to replicate the voluntary ethanol drinking data previously from our laboratory. Finally, immediately after voluntary consumption all mice were again tested for self-administration of 10% ethanol. Alterations in the reinforcement schedule were also explored as RII,+/+ and RII,,/, mice were tested for self-administration of 10% ethanol at FR-3 and FR-5 schedules. Results: The RII,,/, mice displayed lower operant responding for ethanol and food reinforcement compared with RII,+/+ controls. However, this effect was driven by a significant increase in lever responses made by female RII,+/+ mice. When the excessive lever responses of the female RII,+/+ mice are accounted for, the RII,,/, mice show ethanol lever responses comparable to controls. Following operant self-administration testing, RII,,/, mice of both sexes consumed more ethanol solution compared with RII,+/+ mice during 2-bottle testing. Conclusions: Increased ingestion of ethanol by RII,,/, mice is likely the result of altered PKA activity within neuronal pathways that control ethanol-consummatory behaviors. Conversely, the RII, subunit of PKA appears not to play a critical role in neuronal pathways that regulate appetitive behaviors directed at obtaining ethanol. Finally, increased operant self-administration of food and ethanol by female wild-type mice was absent in female RII,,/, mice, suggesting that normal PKA signaling may be part of a general, and sex-dependent, mechanism involved with reinforcement-seeking behavior. [source]


PRECLINICAL STUDY: Conditioned cues and yohimbine induce reinstatement of beer and near-beer seeking in Long-Evans rats

ADDICTION BIOLOGY, Issue 2 2009
Jemma K. Richards
ABSTRACT Alcohol use disorders (AUDs) impact millions of individuals, yet there are few effective treatments. One major problem in treating AUDs is the high rate of relapse to drinking often induced by stress and/or anxiety states. Although beer accounts for over 81% of all alcohol consumed in hazardous amounts in the United States, the use of beer in pre-clinical research has been limited. It has been shown that rats will self-administer beer and near-beer using a standard operant self-administration paradigm; however, there have been few studies examining reinstatement of beer and near-beer seeking. We have determined that reward-associated cues and/or yohimbine will induce reinstatement of beer and near-beer seeking in a similar manner to that seen for 10% ethanol and sucrose seeking using standard operant self-administration and reinstatement paradigms. We show that rats will self-administer beer, near-beer and 4.5% ethanol using an operant self-administration paradigm and both conditioned cues, and yohimbine will induce reinstatement of beer, near-beer and 4.5% ethanol seeking in previously extinguished animals. This demonstrates that both environmental cues and yohimbine-stress will reinstate beer and near-beer seeking, as previously shown for both 10% ethanol and sucrose seeking. [source]


Behavioural sensitization and enhanced dopamine response in the nucleus accumbens after intravenous cocaine self-administration in mice

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003
Agustin Zapata
Abstract The behavioural effects of cocaine are enhanced in animals with a prior history of repeated cocaine administration. This phenomenon, referred to as sensitization, is also associated with an increase in cocaine-evoked extracellular dopamine levels in the nucleus accumbens. Behavioural and neurochemical sensitization has been demonstrated in rats with a prior history of cocaine self-administration and in those that had received experimenter-administered cocaine. Although it is clear that the repeated non-contingent administration also results in behavioural sensitization in the mouse, the issue of whether behavioural and neurochemical sensitization also occur in this species following intravenous cocaine self-administration has not been assessed. The present study used the technique of in vivo microdialysis in conjunction with operant self-administration to characterize cocaine-evoked locomotor activity and dopamine levels in the nucleus accumbens in mice with a prior history of intravenous cocaine self-administration or those that had received yoked infusions of cocaine. Mice that had received contingent or non-contingent infusions of cocaine exhibited an enhanced behavioural response to cocaine and increased cocaine-evoked dopamine levels in the nucleus accumbens. There was no difference between groups in the magnitude of this effect. Prior exposure to cocaine did not modify baseline dopamine levels in the nucleus accumbens. These data demonstrate that mice with previous cocaine self-administration experience show an enhanced behavioural and dopamine response to cocaine in the nucleus accumbens. Furthermore, control over cocaine infusion does not significantly alter the magnitude of the sensitized behavioural and presynaptic dopamine responses observed in response to a challenge dose of cocaine. [source]


Suppression of Heavy Drinking and Alcohol Seeking by a Selective ALDH-2 Inhibitor

ALCOHOLISM, Issue 11 2009
Maria P. Arolfo
Background:, Inherited human aldehyde dehydrogenase 2 (ALDH-2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH-2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH-2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However, daidzin can reduce drinking in some rodents without necessarily increasing acetaldehyde. Therefore, a selective ALDH-2 inhibitor might affect other metabolic factors involved in regulating drinking. Methods:, Aldehyde dehydrogenase 2 inhibitors were synthesized based on the co-crystal structure of ALDH-2 and daidzin. We tested the efficacy of a highly selective reversible ALDH-2 inhibitor, CVT-10216, in models of moderate and high alcohol drinking rats. We studied 2-bottle choice and deprivation-induced drinking paradigms in Fawn Hooded (FH) rats, operant self-administration in Long Evans (LE), FH, and inbred P (iP) rats and in cue-induced reinstatement in iP rats. We also assayed blood acetaldehyde levels as well as dopamine (DA) release in the nucleus accumbens (NAc) and tested possible rewarding/aversive effects of the inhibitor in a conditioned place preference (CPP) paradigm. Results:, CVT-10216 increases acetaldehyde after alcohol gavage and inhibits 2-bottle choice alcohol intake in heavy drinking rodents, including deprivation-induced drinking. Moreover, CVT-10216 also prevents operant self-administration and eliminates cue-induced reinstatement of alcohol seeking even when alcohol is not available (i.e., no acetaldehyde). Alcohol stimulates DA release in the NAc, which is thought to contribute to increased drinking and relapse in alcoholism. CVT-10216 prevents alcohol-induced increases in NAc DA without changing basal levels. CVT-10216 does not show rewarding or aversive properties in the CPP paradigm at therapeutic doses. Conclusion:, Our findings suggest that selective reversible ALDH-2 inhibitors may have therapeutic potential to reduce excessive drinking and to suppress relapse in abstinent alcoholics. [source]


Early Social Isolation in Male Long-Evans Rats Alters Both Appetitive and Consummatory Behaviors Expressed During Operant Ethanol Self-Administration

ALCOHOLISM, Issue 2 2009
Brian A. McCool
Background:, Postweaning social isolation in rats produces profound and long-lasting cognitive and behavioral deficits in adult animals. Importantly, this housing manipulation alters sensitivity to a number of drugs of abuse including ethanol. However, most studies with ethanol have utilized continuous or limited home-cage access to examine interactions between juvenile social experience and drinking. More recently, social isolation was shown to increased ethanol responding in a "dipper" model of self-administration (Deehan et al., 2007). In the current study, we utilize a "sipper" operant self-administration model to distinguish the effects of isolation rearing on ethanol seeking- and drinking-related behaviors. Methods:, Postweaning juvenile male Long-Evans rats were placed into 2 housing groups for 6 weeks: one group consisted of individually housed animals; the second group was housed 4 animals per cage. Following the isolation period, anxiety-like behavior was assessed to confirm the efficacy of the isolation procedure. In some animals, ethanol drinking in the home cage was assessed using a continuous access, 2-bottle choice paradigm. All animals were then individually housed and trained to lever-press for a sipper tube containing either an ethanol solution or a sucrose solution. Results:, Postweaning social isolation increased the expression of anxiety-like behavior in the elevated plus maze but not the light-dark box. Ethanol consumption was also increased during continuous home-cage access with the 2-bottle choice paradigm. During operant self-administration, isolation housing increased the response rate and increased ethanol consumption but did not alter responding for or consumption of sucrose. The housing manipulation did not change the total number of lever responses during extinction sessions. Paired-pulse inhibition deficits that are characteristic of juvenile isolation remained intact after prolonged experience with sucrose self-administration. Discussion:, The effects of postweaning social isolation on ethanol drinking in the home cage are also manifest during operant self-administration. Importantly, these alterations in adult operant self-administration are ethanol-specific. [source]


The Alcohol Deprivation Effect in C57BL/6J Mice is Observed Using Operant Self-Administration Procedures and is Modulated by CRF-1 Receptor Signaling

ALCOHOLISM, Issue 1 2009
Dennis R. Sparta
Background:, The alcohol deprivation effect (ADE) is characterized by transient excessive alcohol consumption upon reinstatement of ethanol following a period of ethanol deprivation. While this phenomenon has been observed in rats using both bottle drinking (consummatory behavior) and operant self-administration (consummatory and appetitive "ethanol-seeking" behavior) procedures, ADE studies in mice have primarily relied on bottle drinking measures. Furthermore, the neurochemical pathways that modulate the ADE are not well understood. Therefore, we determined whether the ADE can be observed in C57BL/6J mice using operant self-administration procedures and if expression of the ADE is modulated by the corticotropin releasing factor-1 (CRF-1) receptor. Methods:, C57BL/6J mice were trained in a 2-hour operant self-administration paradigm to lever press for 10% ethanol or water on separate response keys. Between operant sessions, mice had access to ethanol in their homecage. Once stable responding occurred, mice were deprived of ethanol for 4 days and were then retested with ethanol in the operant paradigm for 3 consecutive days. Next, to assess the role of the CRF-1 receptor, mice were given intraperitoneal (i.p.) injection (0, 10, or 20 mg/kg) of the CRF-1 receptor antagonist CP-154,526 30 minutes before ADE testing. Additional experiments assessed (i) ADE responding in which the alternate response lever was inactive, (ii) the effects of CP-154,526 on self-administration of a 1% sucrose solution following 4 days of deprivation, and (iii) ADE responding in which mice did not received i.p. injections throughout the experiment. Results:, Mice exhibited a significant increase in postdeprivation lever responding for ethanol with either a water reinforced or inactive alternate lever. Interestingly, i.p. injection of a 10 mg/kg dose of CP-154,526 protected against the ADE while not affecting lever responding for a sucrose solution. Finally, baseline and deprivation-induced increases of ethanol reinforced lever responding were greater in mice not given i.p. injections. Conclusions:, The ADE in C57BL/6J mice can be modeled using the operant self-administration paradigm and increased ethanol self-administration associated with the ADE is modulated by CRF-1 receptor signaling. [source]


Increased Consumption but Not Operant Self-administration of Ethanol in Mice Lacking the RII, Subunit of Protein Kinase A

ALCOHOLISM, Issue 5 2006
Frank M. Ferraro III
Background: Accumulating evidence indicates that adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is involved in the neurobiological responses to ethanol. Previous reports indicate that mice lacking the RII, subunit of PKA (RII,,/,) voluntarily consume more ethanol than wild-type controls (RII,+/+) using 2-bottle testing procedures. Although such procedures primarily measure consummatory behavior, operant self-administration procedures allow analysis of consummatory as well as appetitive or "ethanol-seeking" behavior (i.e., lever pressing is required to gain access to the ethanol solution). Therefore, we determined whether the high ethanol consumption characteristic of RII,,/, mice would be complemented by increased appetitive ethanol-seeking behavior in an operant paradigm. Methods: RII,,/, (n=8) and RII,+/+ (n=8) mice were initially sucrose-faded until they were lever responding for nonsweetened ethanol (10, 14, and 18%). Following the self-administration testing, RII,+/+ and RII,,/, mice were given access to 2 bottles, one containing water and the other ethanol to replicate the voluntary ethanol drinking data previously from our laboratory. Finally, immediately after voluntary consumption all mice were again tested for self-administration of 10% ethanol. Alterations in the reinforcement schedule were also explored as RII,+/+ and RII,,/, mice were tested for self-administration of 10% ethanol at FR-3 and FR-5 schedules. Results: The RII,,/, mice displayed lower operant responding for ethanol and food reinforcement compared with RII,+/+ controls. However, this effect was driven by a significant increase in lever responses made by female RII,+/+ mice. When the excessive lever responses of the female RII,+/+ mice are accounted for, the RII,,/, mice show ethanol lever responses comparable to controls. Following operant self-administration testing, RII,,/, mice of both sexes consumed more ethanol solution compared with RII,+/+ mice during 2-bottle testing. Conclusions: Increased ingestion of ethanol by RII,,/, mice is likely the result of altered PKA activity within neuronal pathways that control ethanol-consummatory behaviors. Conversely, the RII, subunit of PKA appears not to play a critical role in neuronal pathways that regulate appetitive behaviors directed at obtaining ethanol. Finally, increased operant self-administration of food and ethanol by female wild-type mice was absent in female RII,,/, mice, suggesting that normal PKA signaling may be part of a general, and sex-dependent, mechanism involved with reinforcement-seeking behavior. [source]