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  • 1
    Electronic Resource
    Electronic Resource
    Central blockade of muscarinic cholinergic receptors disrupts affective and attentional set-shifting (2004)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 20 (2004), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Impairments in multiple aspects of attentional and executive function follow damage to cholinergic neurons in the central nervous system. Affective and attentional set-shifting represent two aspects of executive function controlled by different sectors of the prefrontal cortex. The involvement of cholinergic neural mechanisms in these aspects of executive function has not been specified. To determine whether central muscarinic cholinergic receptors were involved in affective and/or attentional set-shifting, we tested rats on a series of discrimination learning problems, which included affective (reversal learning) and attentional set (extradimensional shift)-shifting components, under the systemic influence of scopolamine, a muscarinic antagonist. Scopolamine impaired both reversal learning and extradimensional shifting, but was without effect on learning new discrimination problems that did not require an affective or attentional shift. Systemic administration of methylscopolamine, which does not cross the blood–brain barrier, did not impair affective or attentional set-shifting, indicating that the scopolamine effects were centrally mediated. These data implicate muscarinic receptors in the central nervous system in the control of executive function. Taken together with other recent data, they may also suggest an important role for cholinergic receptors outside of the neocortex in regulating these aspects of attention and executive function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2004.03548.x
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  • 2
    Electronic Resource
    Electronic Resource
    PDE10A inhibition reverses subchronic PCP-induced deficits in attentional set-shifting in rats (2005)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 21 (2005), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Persistent suppression of N-methyl-d-aspartate (NMDA) receptor function produces enduring structural changes in neocortical and limbic regions in a pattern similar to changes reported in schizophrenia. This similarity suggests that chronic NMDA receptor antagonism in animals may represent a useful model of neurobiological and related cognitive deficits in schizophrenia. Schizophrenia is associated with impairments in frontal lobe-dependent cognitive functions, including working memory and attentional shifting. Deficits in attention and executive function have not been well characterized in animal models of schizophrenia using chronic NMDA receptor antagonist administration. We investigated whether subchronic systemic administration of the NMDA receptor antagonist phencyclidine (PCP) to rats followed by a drug washout period would produce enduring cognitive deficits on an attentional set-shifting task. The task is functionally analogous to a sensitive test of frontal function in humans and non-human primates. Subchronic PCP administration selectively impaired extradimensional shift learning without affecting other discrimination or reversal tasks. Moreover, acute treatment with the PDE10A inhibitor papaverine immediately prior to testing attenuated the PCP-induced deficits in extradimensional shift learning across a range of doses. These data suggest that subchronic PCP administration may model effectively some of the cognitive deficits that are observed in schizophrenia, and that PDE10A inhibition may be an effective therapeutic route to improve executive function deficits associated with schizophrenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2005.03937.x
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  • 3
    Electronic Resource
    Electronic Resource
    Naltrexone pretreatment decreases the reinforcing effectiveness of ethanol and saccharin but not PCP or food under concurrent progressive-ratio schedules in rhesus monkeys (1999)
    Springer
    Psychopharmacology 141 (1999), S. 436-446 
    Details
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Food ; Monkey ; Oral ; Phencyclidine ; Progressive ratio ; Saccharin ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of this experiment was to determine whether attenuation of ethanol consumption by naltrexone is the result of selective changes in the reinforcing effectiveness of drug and non-drug reinforcers. A range of naltrexone doses (0.1–1.0 mg/kg) was administered for 5 days, and the effects on the reinforcing effects of orally delivered 8% (w/v) ethanol, 0.25 mg/ml phencyclidine (PCP), 0.03% (w/v) saccharin and food were studied in eight rhesus monkeys. Food and liquids were available under independent and concurrent progressive-ratio (PR) schedules (ratio range 8–4096) during daily 3-h sessions. Ethanol-maintained responding was attenuated by 0.3 and 1.0 mg/kg doses of naltrexone, while saccharin-maintained responding was decreased at the 1.0 mg/kg dose. Furthermore, there was a significant linear trend that consumption of available ethanol and saccharin was attenuated dose-dependently by naltrexone. Following 5 days of naltrexone pretreatment, ethanol- and saccharin-maintained responding immediately returned to or exceeded baseline levels. Food- and PCP-maintained responding and intake were not significantly affected by any of the naltrexone doses examined. The decreased break point (BP) values for ethanol and saccharin suggest that their reinforcing effects are mediated through opioid reinforcement mechanisms. The lack of naltrexone attenuation of PCP- and food-maintained responding suggests that these reinforcers: 1) are not sensitive to naltrexone antagonism at the doses examined, 2) are mediated by non-opioid reinforcement mechanisms, and/or 3) have less intrinsic palatability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050854
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of dopamine receptor antagonists (D1 and D2) on the demand for smoked cocaine base in rhesus monkeys (1999)
    Springer
    Psychopharmacology 144 (1999), S. 381-388 
    Details
    ISSN: 1432-2072
    Keywords: Key words Behavioral economics ; Cocaine base ; Crack ; Demand ; Dopamine antagonist ; Drug self-administration ; Elasticity ; Raclopride ; Rhesus monkey ; SCH 23390 ; Unit price
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Previous studies suggest that dopamine antagonists may reduce the reinforcing effects of cocaine. However, the effects of these antagonists on the demand for smoked cocaine base have not been quantified. Objectives: To evaluate the effects of selective D1 (SCH 23390) and D2 (raclopride) dopamine receptor antagonists on the demand for smoked cocaine base in rhesus monkeys using a behavioral economic analysis. Methods: Six rhesus monkeys were trained to self-administer smoked cocaine base (1.0 mg/kg/delivery) under chained fixed-ratio (FR) schedules (FR64, 128, 256, 512, 1024 or 2048 for lever presses and FR5 for inhalations) during daily 4-h sessions. A maximum of ten smoke deliveries were available. After 5 days of stable behavior at each FR, SCH 23390 (0.01 and 0.056 mg/kg) or raclopride (0.03 and 0.056 mg/kg) were injected intramuscularly, before each session, for 3 consecutive days. Results: Pretreatment with both antagonists dose-dependently reduced cocaine intake across most FR values tested; however, the decrease in consumption was greater at the higher unit prices than at the lower unit prices. A statistical estimate of the price (FR) at which maximum responding occurred (Pmax) was decreased during drug pretreatment, indicating weakened reinforcing effectiveness of cocaine. Conclusions: These data suggest that both antagonists reduce the reinforcing effectiveness of smoked cocaine base, and they have a greater effect on cocaine consumption at higher FR values.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130051021
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  • 5
    Electronic Resource
    Electronic Resource
    Concurrent progressive-ratio schedules to compare reinforcing effectiveness of different phencyclidine (PCP) concentrations in rhesus monkeys (1999)
    Springer
    Psychopharmacology 144 (1999), S. 163-174 
    Details
    ISSN: 1432-2072
    Keywords: Key words Concentration ; Concurrent schedules ; Monkey ; Oral ; Phencyclidine (PCP) ; Progressive ratio ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Progressive ratio (PR) schedules have become well accepted for testing the reinforcing effectiveness of drugs. This study extends the methods to concurrent PR schedules with different concentrations of orally delivered phencyclidine (PCP). Objective: The sensitivity of the procedure is tested by presenting different PCP concentrations with independently-operating PR schedules. Method: PCP self-administration was investigated in seven rhesus monkeys. Six different PCP concentrations (0.03–1.0 mg/ml) and water were randomly paired (21 pairings). Liquid delivery (24 ml) was contingent upon lip-contact responses on solenoid-operated drinking spouts; whereby, the response requirement or fixed-ratio (FR) increased (from 8 to 16, 32, 64, 128... to 4096) after each successful completion of a previous FR and subsequent liquid delivery. Monkeys self administered PCP during daily 3-h sessions, and each pair of concentrations was held constant until behavior had stabilized for at least 4 days. Results: The higher of the two PCP concentrations always maintained greater responding, PR break point (BP), or the last ratio completed, and liquid deliveries than did the lower concentration. However, the monkeys did not exclusively respond on the drinking spout that yielded the higher drug concentration. When examined across all drug pairings, the percentage of total available deliveries of the higher concentration was significantly greater than those of the lower concentration. The monkeys maximized the amount (mg) consumed for the response output. Responding, BPs and liquid deliveries maintained by 0.12 and 0.25 mg/ml PCP were significantly greater than other PCP concentrations; however, drug intake (mg) increased directly with PCP concentration. Conclusion: These results indicate that concurrent PR schedules using oral drug self-administration and a concurrent choice paradigm reliably provide an estimation of relative reinforcing strength, and behavior maintained by these schedules is sensitive to small changes in PCP concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050990
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  • 6
    Electronic Resource
    Electronic Resource
    A comparison of progressive ratio schedules versus behavioral economic measures: effect of an alternative reinforcer on the reinforcing efficacy of phencyclidine (1997)
    Springer
    Psychopharmacology 132 (1997), S. 95-103 
    Details
    ISSN: 1432-2072
    Keywords: Key words Alternative reinforcer ; Behavioral economics ; Break point ; Drug-reinforced behavior ; Drug self-administration ; Phencyclidine ; Progressive ratio ; Reinforcing efficacy ; Rhesus monkeys ; Saccharin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Alternative non-drug reinforcers have been demonstrated to decrease drug-reinforced behavior by both decreasing relative reinforcing efficacy and substituting for the drug reinforcer. The effect of saccharin on responding maintained by orally delivered phencyclidine (PCP) was examined in this study using concurrent progressive-ratio (PR) schedules of reinforcement and a behavioral economic analysis of demand. Seven adult male rhesus monkeys self-administered PCP (0.06, 0.12, 0.25, 0.50 and 1.0 mg/ml) and either concurrent water or saccharin (0.03% wt/vol) from two drinking spouts under concurrent independent PR schedules. During daily sessions the response requirements (lip contacts on automatic drinking spouts) increased across 15 levels, from 8 to 4096. Each successful ratio completion resulted in the availability of 40 liquid deliveries under an FR 1 schedule and a subsequent increment in the PR. Concentrations of PCP were presented in a non-systematic order and presentation of the concurrent liquid, saccharin or water, was counterbalanced across subjects. All behaviors maintained by PCP were significantly greater than those maintained by water. Replacement of water with saccharin served to significantly decrease PCP-maintained responding and break points (BP) across the range of PCP concentrations; however, saccharin did not significantly decrease deliveries of PCP. Saccharin maintained significantly greater responding, BPs and deliveries compared to either PCP or water, across all PCP concentrations. The use of BP as a measure of reinforcing efficacy suggests that saccharin decreased the relative reinforcing efficacy of PCP. Furthermore, behavioral economic analyses suggested that saccharin decreased maximal PCP-maintained responding (Pmax) in a similar fashion, suggesting that BP and Pmax may be analogous measures of reinforcing efficacy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050325
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