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  • 1
    Electronic Resource
    Electronic Resource
    Periodic acid-Schiff(PAS)-positive deposits in brain following kainic acid-induced seizures: relationships to fos induction, neuronal necrosis, reactive gliosis, and blood-brain barrier breakdown (1995)
    Springer
    Acta neuropathologica 89 (1995), S. 126-138 
    Details
    ISSN: 1432-0533
    Keywords: Neurodegeneration ; Epilepsy ; Kainic acid fos ; Gliosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Periodic acid-Schiff (PAS)-positive deposits have been demonstrated in the central nervous system (CNS) of patients suffering from a wide variety of neurodegenerative disorders including Alzheimer's disease, presenile dementia, Parkinson's disease, diabetes mellitus, myoclonic epilepsy, and cerebral palsy. The etiology of these deposits and their relationship to mechanisms of progressive neurodegeneration is unknown. In the present study, we demonstrate that the kainic acid model of limbic status epilepticus provides a useful system for the study of PAS-positive staining. The relationship between PAS-positive deposition, induction of fos-like immunoreactivity (FLI), neuronal necrosis, reactive gliosis, and blood-brain barrier breakdown following the kainic acid induction of status epilepticus was investigated. Epileptiform activity was elicited in rats by intraperitoneal administration of 10 mg/kg kainic acid and brains were examined 3, 5, 12, 24, 72, and 168 h after drug injection. Four distinct types of PAS-positive staining in rat brain were observed: type 1, extracellular matrix (ECM) or blood vessel associated-material; type 2, granular deposits; type 3, glial labelling; and type 4, neuronal labelling. Results demonstrated that the four types of PAS-positive staining were differentially associated with specific markers of neuropathology: (1) type 1 ECM staining and type 3 glia were preferentially localized to edematous tissue; (2) the majority of type 3 glia were identified as reactive astrocytes, while a minority of appeared to be proliferating microglia; (3) type 1 blood vessels labelled hemorrhaging vasculature; (4) early deposition of type 2 granules was predictive of subsequent cell loss; (5) chronic type 2 granular deposits and type 4 neuronal labelling not associated with cell death could be predicted by early changes in FLI; and (6) chronic deposition of all four forms of PAS-positive material was correlated with earlier, transient blood-brain barrier compromise. The results support the growing literature that local carbohydrate metabolism may be one of a constellation of parameters important to the development of progressive neurodegeneration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296356
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  • 2
    Electronic Resource
    Electronic Resource
    The estrous cycle affects cocaine self-administration on a progressive ratio schedule in rats (1989)
    Springer
    Psychopharmacology 98 (1989), S. 408-411 
    Details
    ISSN: 1432-2072
    Keywords: Gender ; Estrous cycle ; Cocaine self-administration ; Fixed ratio one ; Progressive ratio schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although it has been demonstrated that many of the behavioral responses to psychomotor stimulants are gender dependent and hormonally sensitive, few studies have examined the possibility that the estrous cycle interacts with drug reinforcement in laboratory animals. The present experiment assessed the effect of the estrous cycle on two aspects of cocaine self-administration behavior: the breaking point on a progressive ratio (PR) schedule and the rate of cocaine intake on a fixed ratio one (FR1) schedule. On the PR schedule, the first lever response produced a drug infusion. Subsequent response requirements escalated with each injection until the behavior extinguished. Breaking points were defined as the final ratio completed. On a FR1 schedule, the estrous cycle had no effect on the rate of drug intake. On a PR schedule, female rats reached higher breaking points during estrus than during other stages of the estrous cycle. Furthermore, female rats displayed higher breaking points than male rats. It appears that the estrous cycle influences an animal's motivation to self-administer cocaine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00451696
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of (−)-DS 121 and (+)-UH 232 on cocaine self-administration in rats (1995)
    Springer
    Psychopharmacology 120 (1995), S. 93-98 
    Details
    ISSN: 1432-2072
    Keywords: (−)-DS 121 ; (+)-UH232 ; Cocaine ; Rats ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The novel dopamine autoreceptor antagonists (−)-DS 121 and (+)-UH 232 were tested for their ability to alter cocaine self-administration behavior in rats reinforced on a progressive ratio (PR) schedule. (−)-DS 121 (15 mg/kg) and (+)-UH 232 (30 mg/kg) produced significant decreases in breaking point. (−)-DS 121 produced variable results on rate of cocaine intake on an FR1 schedule, indicating that rate may on occasion be insensitive to changes in cocaine reinforcement. In animals previously trained to self-administer cocaine, (−)-DS 121 failed to maintain responding when substituted for cocaine. This profile suggests that (−)-DS 121 is a promising new candidate for the treatment of cocaine abuse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246149
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  • 4
    Electronic Resource
    Electronic Resource
    Oral self-administration of sweetened nicotine solutions by rats (1995)
    Springer
    Psychopharmacology 120 (1995), S. 341-346 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Self-administration ; Oral intake ; Behavioral economics ; Sucrose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oral self-administration of sweetened nicotine solutions in rats was studied in two ways. In the first experiment, one group had continuous access to a water bottle containing a sucrose solution and nicotine (10 µg/ml), while another group had access to an identical sucrose solution without nicotine. All rats had continuous access to water. While consumption of nicotine increased with increasing concentrations of sucrose, consumption of the sucrose + nicotine solution never exceeded the intake of sucrose alone. In subsequent experiments, the delivery of the solutions was made contingent upon an operant response. The sucrose + nicotine solution was found to maintain responding to higher response/reinforcer ratiosthan the sucrose only solution. These data demonstrate that rats will self-administer sweetened nicotine solutions and that sucrose + nicotine solutions are more reinforcing than sucrose solutions alone. Free accessconsumption is not a good predictor of the response maintaining properties of nicotine solutions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02311182
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  • 5
    Electronic Resource
    Electronic Resource
    Self-administration of cocaine analogs by rats (1999)
    Springer
    Psychopharmacology 144 (1999), S. 389-397 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Tropane analogs ; Self-administration ; Progressive-ratio schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: A novel scheme for the synthesis of cocaine analogs from vinylcarbenoid precursors has made available compounds that have a diverse range of affinities for the DA and 5-HT transporters. These compounds were used to explore the relationship between their biochemical properties and their reinforcing effects. Objectives: The objective was to assess the reinforcing efficacy of selected cocaine analogs and compare the results with their selectivity in binding to DA and 5-HT transporters. Methods: Rats were prepared with chronically indwelling intravenous cannulae and trained to self-administer cocaine on a progressive ratio (PR) schedule. A range of doses of seven cocaine analogs were substituted for cocaine in separate groups of animals. Results: The results demonstrate a wide range of reinforcing efficacies and potencies among the seven selected drugs. Four tropane analogs (WF-11, WF-23, WF-24, WF-55) were found to support self-administration behavior on a PR schedule while three did not (WF-31, WF-54 and WF-60). The DA/5-HT selectivity ratio was found to be a better predictor of self-administration behavior than affinity at the DA transporter alone. Conclusion: These data suggest that drugs with a higher affinity for the DA versus the 5-HT transporter are more likely to be self-administered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130051022
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  • 6
    Electronic Resource
    Electronic Resource
    Effect of baclofen on cocaine self-administration in rats reinforced under fixed-ratio 1 and progressive-ratio schedules (2000)
    Springer
    Psychopharmacology 148 (2000), S. 314-321 
    Details
    ISSN: 1432-2072
    Keywords: Key words Baclofen ; Cocaine ; GABA ; Self-administration ; Reward
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Recent reports have indicated that the γ-aminobutyric acid (GABA)B agonist baclofen attenuates the reinforcing effects of cocaine. Objectives: To further evaluate the effect of baclofen on cocaine self-administration under a fixed ratio (FR) and progressive ratio (PR) schedule of reinforcement. Methods: In the first series of experiments, three dose–response curves were generated that examined the effect of three doses of baclofen (1.8, 3.2, or 5.6 mg/kg, i.p.) against four unit-injection doses of cocaine (0.19, 0.38, 0.75, and 1.5 mg/kg per injection) reinforced under a FR1 schedule. For comparison, an additional group of rats was pretreated with haloperidol (32, 56, or 100 µg/kg, i.p.). A separate experiment examined the effect of baclofen (1.8, 3.2, or 5.6 mg/kg, i.p.) on responding for concurrently available cocaine or food reinforcement. Results: Under the FR1 schedule, baclofen suppressed intake of low but not high unit injection doses of cocaine. In contrast to haloperidol, baclofen had no effect on the distribution of inter-injection intervals and, instead, produced long pauses in cocaine self-administration. Baclofen dose dependently reduced cocaine- reinforced responding on a PR schedule; concurrent access to a food-reinforced lever demonstrated that the animals retained the capacity to respond at high rates. Conclusion: The effect of baclofen pretreatment on cocaine self-administration is dependent on the unit injection dose of cocaine and on the response requirements of the schedule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050056
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  • 7
    Electronic Resource
    Electronic Resource
    Systemic pretreatment with MK-801 (dizocilpine) increases breaking points for self-administration of cocaine on a progressive-ratio schedule in rats (1996)
    Springer
    Psychopharmacology 128 (1996), S. 83-88 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; MK-801 ; Progressive-ratio schedule ; Reinforcement ; Reward ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effects of the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, on cocaine self-administration were investigated. Forty-six male Wistar rats were trained to intravenously self-administer four unit doses of cocaine (0.19, 0.38, 0.75 and 1.5 mg/kg per injection) on a progressive-ratio schedule of reinforcement. The effects of increasing doses of MK-801 (0.05, 0.1, 0.15 and 0.2 mg/kg, IP, 30 min before test sessions) on breaking point (BP) for cocaine self-administration were investigated. The results showed that pretreatment with MK-801 produced effects on cocaine BPs that fit on an inverted-U function. That is, the 0.05 and 0.1 mg/kg doses of MK-801 produced no effect or a small enhancement of BPs across all doses of cocaine, respectively. The 0.15 mg/kg dose of MK-801 produced a significant treatment effect characterized by increased BPs, relative to baseline BPs, across all doses of cocaine. The 0.2 mg/kg dose of MK-801 produced a nonsignificant decrease in BPs across most doses of cocaine. The dose-dependent effects on cocaine BPs after pretreatment with MK-801 suggest that MK-801 can potentiate, and at higher doses attenuate, the rewarding effects of self-administered cocaine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050113
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  • 8
    Electronic Resource
    Electronic Resource
    The effect of haloperidol on cocaine self-administration is augmented with repeated administrations (1987)
    Springer
    Psychopharmacology 93 (1987), S. 526-528 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Self-administration ; Haloperidol ; Neuroleptic drugs ; Behavioral screen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Administration of haloperidol (0.075 mg/kg) prior to a 4-h self-administration session increases cocaine intake by male rats. Animals pretreated daily with haloperidol showed a significant augmentation of this response, with cocaine intake climbing from 37% above baseline to 65% above baseline in 7 days. Control rats given two treatments of haloperidol 7 days apart showed no augmentation of the response. This increased drug effect is unusual, since most behavioral actions of haloperidol in laboratory animals show tolerance. In humans, the antipsychotic activity of neuroleptic drugs requires many days to develop. Cocaine self-administration behavior might therefore provide a model for antipsychotic drug action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207247
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  • 9
    Electronic Resource
    Electronic Resource
    Heroin self-administration in rats under a progressive ratio schedule of reinforcement (1993)
    Springer
    Psychopharmacology 111 (1993), S. 215-218 
    Details
    ISSN: 1432-2072
    Keywords: Self-administration ; Progressive ratio ; Heroin ; Dose-response ; Naltrexone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Heroin self-administration behavior under a progressive ratio (PR) schedule of reinforcement was evaluated in rats. The schedule was designed to restrict drug intake, minimize opiate dependency, and quantify the number of responses emitted (final response ratio) in order to receive a limited number of heroin infusions. Final ratios were found to be stable and did not increase with chronic (31 days) PR reinforcement. The ability of the PR schedule to detect changes in heroin reinforcement was demonstrated by evaluating the effect of naltrexone pretreatment and unit dose alteration on final ratios. Naltrexone (0.4 mg/kg) reduced final ratios and an inverted U dose-response relationship was established for the unit heroin doses 12.5–100 µg/injection. Maximal final ratios occurred with 50 µg/injection heroin reinforcement. This PR schedule may provide a useful method for evaluating the effects of pharmacological manipulations or lesions on opiate reinforcement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245526
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  • 10
    Electronic Resource
    Electronic Resource
    Baclofen suppression of cocaine self-administration: demonstration using a discrete trials procedure (1997)
    Springer
    Psychopharmacology 131 (1997), S. 271-277 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Self-administration ; Baclofen ; Discrete trials procedure ; GABA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that rats display a circadian pattern of cocaine self-administration if access to drug is limited to 10-min discrete trials that are separated by at least 20 min. In the present study, the pattern of cocaine intake (1.5 mg/kg per injection) was studied in two large groups of animals that were maintained on different 12-h light/dark cycles (3 a.m. to 3 p.m. versus 10 a.m. to 10 p.m.). Regardless of the time of light onset, a circadian pattern of cocaine self-administration was observed. Maximum cocaine intake occurred during the final 6 h of the dark period and was followed by a relative abstinence period during the light phase. This highly predictable pattern of drug taking behavior provided an opportunity to explore the effect of baclofen, a GABAB agonist, on the initiation of self-administration behavior. In two separate studies, acute treatment with baclofen (1.25–5.0 mg/kg) was shown to suppress cocaine intake for at least 4 h. Baclofen had no significant effect on responding for food reinforcement. Previous results have indicated that baclofen appears to reduce specifically the motivation to respond for cocaine. Together, these data suggest that baclofen should be considered as a possible pharmacotherapeutic agent in cocaine addiction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050293
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