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  • 1
    Electronic Resource
    Electronic Resource
    Chronic cocaine-mediated changes in non-human primate nucleus accumbens gene expression (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 77 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Chronic cocaine use elicits changes in the pattern of gene expression within reinforcement-related, dopaminergic regions. cDNA hybridization arrays were used to illuminate cocaine-regulated genes in the nucleus accumbens (NAcc) of non-human primates (Macaca fascicularis; cynomolgus macaque), treated daily with escalating doses of cocaine over one year. Changes seen in mRNA levels by hybridization array analysis were confirmed at the level of protein (via specific immunoblots). Significantly up-regulated genes included: protein kinase A α catalytic subunit (PKAcα); cell adhesion tyrosine kinase beta (PYK2); mitogen activated protein kinase kinase 1 (MEK1); and β-catenin. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. All of these adaptive responses coexist within a signaling scheme that could account for known inductions of genes(e.g. fos and jun proteins, and cyclic AMP response element binding protein) previously shown to be relevant to cocaine's behavioral actions. The complete data set from this experiment has been posted to the newly created Drug and Alcohol Abuse Array Data Consortium () for mining by the general research community.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.00252.x
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  • 2
    Electronic Resource
    Electronic Resource
    Chronic cocaine-mediated changes in non-human primate nucleus accumbens gene expression (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 77 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.00382.x
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Behavioral and Pharmacological Determinants of Drug Abuse (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 654 (1992), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1992.tb25982.x
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of increasing the magnitude of an alternative reinforcer on drug choice in a discrete-trials choice procedure (1991)
    Springer
    Psychopharmacology 105 (1991), S. 169-174 
    Details
    ISSN: 1432-2072
    Keywords: Choice ; Self-administration ; Cocaine ; Procaine ; Rhesus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rhesus monkeys were trained in a discretetrials choice procedure and allowed to choose between food delivery (1–16 pellets; 1 g/pellet) and intravenous injections of cocaine (0.03–0.56 mg/kg/injection;N=4) or procaine (1.0–10 mg/kg/injection;N=4) during daily 3-h sessions. Injections were available as the alternative to food. When the amount of food available as the alternative to drug was held constant and dose of drug was varied, the frequency of drug choice and total drug intake increased in a dose-related fashion for both cocaine and procaine. For both drugs, when the amount of food available as the alternative to drug was increased and the dose of the drug was held constant, the frequency of drug choice and total drug intake decreased. Thus, increases in the magnitude of an alternative non-drug reinforcer decreased cocaine and procaine self-administration. Further, the results suggest that while increasing the magnitude of the alternative reinforcer decreased the potency of cocaine as a positive reinforcer, the reinforcing efficacy of procaine was decreased. Because drug use by humans typically occurs in a context in which other reinforcers are available, the present results are consistent with the hypothesis that drug self-administration by humans can be decreased by increasing the value of alternative positive reinforcers. In addition, these results suggest that the extent to which drug self-administration is sensitive to this manipulation varies across drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244304
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of increasing response requirement on choice between cocaine and food in rhesus monkeys (1992)
    Springer
    Psychopharmacology 108 (1992), S. 295-300 
    Details
    ISSN: 1432-2072
    Keywords: Discrete-trials choice ; Self-administration ; Cocaine ; Progressive-ratio ; Alternative reinforcer ; Rhesus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rhesus monkeys were trained in a discretetrials choice procedure and allowed to choose between intravenous injections of cocaine (0.01–1.0 mg/kg/injection) and food presentation (1 or 4 pellets; 1 g/pellet) during daily 7-h experimental sessions. When each reinforcer was available under a fixed-ratio (FR) 30 schedule, the frequency of cocaine choice and the total drug intake increased in a dose-related manner for all monkeys. When the FR for cocaine was differentially increased, the frequency of cocaine choice decreased, shifting the cocaine dose-response function to the right and/or downward. When the FR for cocaine was at least 480, cocaine preference could not be recovered up to doses of 1.0 mg/kg/injection. In a second experiment, when the response requirement for food was differentially increased, the frequency of cocaine choice increased. These results demonstrate that altering the response requirement for cocaine or for alternative reinforcers that are available can substantially affect cocaine self-administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245115
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  • 6
    Electronic Resource
    Electronic Resource
    Further evaluation of the reinforcing effects of the novel cocaine analog 2β-propanoyl-3β-(4-tolyl)-tropane (PTT) in rhesus monkeys (1998)
    Springer
    Psychopharmacology 136 (1998), S. 139-147 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Tropanes ; Dopamine transporter ; Self-administration ; Rhesus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  2β-Propanoyl-3β-(4-tolyl)-tropane (PTT) is a cocaine analog which has been shown in rhesus monkeys to have cocaine-like discriminative stimulus effects and a long duration of action (〉8 h), yet does not function as a reinforcer when substituted for cocaine in monkeys responding under a fixed-interval 5-min schedule (Nader et al. 1997). The purpose of the present study was to evaluate the reinforcing effects of PTT under a fixed-ratio (FR) schedule and to determine if decreasing the inter-injection interval would influence the reinforcing effects of PTT. Male rhesus monkeys (n=3) were trained to respond under a multiple FR 30 food-drug-food schedule. When responding was stable, cocaine (0.003–0.3 mg/kg per injection) or PTT (0.001–0.03 mg/kg per injection) was available during the drug component for at least five consecutive sessions and until stable responding was observed. To investigate whether the inter-injection interval would influence PTT-maintained response rates, the time-out (TO) following PTT injections was reduced from 180 or 300 s to 10 s for at least five consecutive sessions. Cocaine-maintained response rates were characterized as an inverted-U shaped function of dose, with peak rates maintained by 0.03 mg/kg per injection cocaine. PTT (0.001–0.03 mg/kg per injection) maintained response rates significantly higher than rates maintained by the PTT vehicle, but significantly lower than cocaine-maintained response rates; PTT intake increased with dose. A reduction of the TO following PTT injections to 10 s did not alter PTT-maintained response rates or total session intake. Self-administered PTT was more potent than cocaine at decreasing food-maintained responding. These results suggest that for long-acting compounds like PTT, reinforcing effects are more likely to be observed when the drug is available under a ratio-based schedule, compared to an interval-based schedule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050549
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  • 7
    Electronic Resource
    Electronic Resource
    The effects of behavioral history on cocaine self-administration by rhesus monkeys (1994)
    Springer
    Psychopharmacology 115 (1994), S. 53-58 
    Details
    ISSN: 1432-2072
    Keywords: Behavioral history ; Self-administration ; Cocaine ; Drug abuse ; Schedule-controlled behavior ; Fixed-ratio ; Inter-response times ; Rhesus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to examine whether a history of responding under schedules that generate either high or low response rates could modify previously established cocaine self-administration. Eight experimentally naive rhesus monkeys were trained to respond on one of two levers under a fixed-interval (FI) 5-min schedule of intravenous cocaine (0.03 mg/kg per injection) presentation. When responding was stable a cocaine dose-response curve (saline, 0.01–0.3 mg/kg per injection) was determined. Following completion of the dose-response curves, the monkeys were randomly assigned to one of two groups (n=4/group) and trained to respond on the other lever under either a fixed-ratio (FR) 50 or inter-response times (IRT) 〉 30-s schedule of cocaine (0.03 mg/kg per injection) presentation. After 65 sessions responding was again maintained under the FI5-min schedule of 0.03 mg/kg per injection cocaine for 60 sessions, followed by redetermination of the cocaine dose-response curve. During the initial exposure to the FI schedule, the mean rate of responding was 4.02 (± 0.33) responses/min and the cocaine dose-response curve was characterized as an inverted-U shape function of dose, with peak responding at 0.03 mg/kg per injection. The FR50 schedule generated high rates (66.80 ± 5.6 responses/min), while response rates under the IRT 〉 30-s schedule were low (2.62 ± 0.2 responses/min). Following different behavioral histories, response rates under the FI5-min schedule were significantly higher for 60 sessions in FR-history monkeys compared to IRT-history subjects. Compared to the initial FI baselines, cocaine intake (mg/kg per session) was significantly higher following an FR-history and significantly lower following training under an IRT schedule, for 60 consecutive sessions. In addition, there was a significant effect of behavioral history on the cocaine dose-response curve, such that descending limb was shifted farther to the right in FR-history subjects compared to IRT-history monkeys. Results from the present study indicate that previously established “drug-seeking” behavior can be modified by training under different reinforcement schedules. Knowledge of such historical variables may be important in understanding the determinants of drug self-administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244751
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    Paper (German National Licenses)
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  • 8
    Electronic Resource
    Electronic Resource
    Discriminative and reinforcing effects of brotizolam in rhesus monkeys (1991)
    Springer
    Psychopharmacology 103 (1991), S. 166-171 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Self-administration ; Brotizolam ; Pentobarbital ; Rhesus monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The reinforcing and discriminative stimulus effects of brotizolam, a benzodiazepine-hypnotic, were evaluated in rhesus monkeys. In one experiment, separate groups of monkeys (N=3/group) were trained to discriminate pentobarbital (10 mg/kg, IG) ord-amphetamine (0.56–1.0 mg/kg, IG) from saline, in a discrete-trials avoidance/escape paradigm. Pentobarbital (5.6–10 mg/kg), diazepam (1.0–1.7 mg/kg), and brotizolam (0.3–1.7 mg/kg) resulted in 100% drug-lever responding in all three pentobarbital-trained monkeys. Ind-amphetamine-trained monkeys brotizolam administration resulted only in saline-lever responding. In another experiment, monkeys were surgically prepared with indwelling intravenous catheters and lever pressing resulted in an injection of 0.1 mg/kg/injection sodium methohexital under a fixed-ratio 10 (FR 10) schedule. Pentobarbital (0.01–0.3 mg/kg/injection) and diazepam (0.003–0.10 mg/kg/injection) maintained responding above saline control levels when substituted for methohexital. Brotizolam (0.001–0.01 mg/kg/injection) resulted in more injections received compared to saline, but fewer injections compared to pentobarbital or diazepam. Thus, results from the present experiment suggest that brotizolam would have pentobarbital-like subjective effects. However, the abuse liability of brotizolam may be lower than that for diazepam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244198
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of different food-reinforcement histories on cocaine self-administration by rhesus monkeys (1995)
    Springer
    Psychopharmacology 118 (1995), S. 287-294 
    Details
    ISSN: 1432-2072
    Keywords: Behavioral history ; Self-administration ; Cocaine ; Drug abuse ; Fixed-interval ; Fixed-ratio ; Interresponse times ; Rhesus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to examine whether a history of responding under food reinforcement schedules that generated either high or low response rates would influence the acquisition and maintenance of cocaine self-administration. Eight experimentally naive rhesus monkeys were initially trained to respond on the right lever under either a fixed-ratio (FR) 50 or interresponse times (IRT) 〉 30-s schedule of food reinforcement. After 65 sessions of food-maintained responding, monkeys were surgically prepared with indwelling intravenous catheters and cocaine 0.03 mg/kg per injection (IV) was available on the left lever under a fixed-interval (FI) 5-min schedule. After at least 60 consecutive sessions at this dose, a cocaine dose-response curve (saline, 0.01–0.3 mg/kg per injection) was determined. The FR 50 schedule generated high rates of food-maintained responding (90.1±6.2 responses/min), while response rates under the IRT 〉30-s schedule were low (1.9±0.1 responses/min). Across the 60 consecutive sessions under the FI 5-min schedule, linear changes in response rates and cocaine intake were significantly different between FR- and IRT-history monkeys. FR-history monkeys responded at higher rates than IRT-history subjects, while cocaine intake during the first 15 sessions was lower in FR- compared to IRT-history monkeys. Rates of cocaine-maintained responding after food-reinforcement histories were compared to response rates of monkeys initially trained to self-administer cocaine under an FI 5-min schedule (Nader and Reboussin 1994). Response rates were higher in this latter group compared to rates generated by either group of monkeys after food-reinforcement histories. Furthermore, a significant interaction between behavioral history and cocaine dose on response rates was observed. Results from the present study indicate that a history of responding maintained by a nondrug reinforcer can have significant and long-lasting effects on response rates and total cocaine intake under an FI schedule. Furthermore, these results indicate that prior experiences may produce different effects on acquisition and maintenance of cocaine self-administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245957
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