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  • 1
    Electronic Resource
    Electronic Resource
    Opposite modulatory roles for adenosine A1 and A2A receptors on glutamate and dopamine release in the shell of the nucleus accumbens. Effects of chronic caffeine exposure (2004)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 88 (2004), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies have demonstrated opposing roles for adenosine A1 and A2A receptors in the modulation of extracellular levels of glutamate and dopamine in the striatum. In the present study, acute systemic administration of motor-activating doses of the A2A receptor antagonist MSX-3 significantly decreased extracellular levels of dopamine and glutamate in the shell of the rat nucleus accumbens (NAc) and counteracted both dopamine and glutamate release induced by systemic administration of motor-activating doses of either the A1 receptor antagonist CPT or caffeine. Furthermore, exposure to caffeine in the drinking water (1 mg/mL, 14 days) resulted in tolerance to the effects of systemic injection of CPT or caffeine, but not MSX-3, on extracellular levels of dopamine and glutamate in the NAc shell. The present results show: first, the existence of opposite tonic effects of adenosine on extracellular levels of dopamine and glutamate in the shell of the NAc mediated by A1 and A2A receptors; second, that complete tolerance to caffeine's dopamine- and glutamate-releasing effects which develops after chronic caffeine exposure is attributable to an A1 receptor-mediated mechanism. Development of tolerance to the dopamine-releasing effects of caffeine in the shell of the NAc may explain its weak addictive properties and atypical psychostimulant profile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.02245.x
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  • 2
    Electronic Resource
    Electronic Resource
    Adenosine receptor-mediated modulation of dopamine release in the nucleus accumbens depends on glutamate neurotransmission and N-methyl-d-aspartate receptor stimulation (2004)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 91 (2004), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Adenosine, by acting on adenosine A1 and A2A receptors, exerts opposite modulatory roles on striatal extracellular levels of glutamate and dopamine, with activation of A1 inhibiting and activation of A2A receptors stimulating glutamate and dopamine release. Adenosine-mediated modulation of striatal dopaminergic neurotransmission could be secondary to changes in glutamate neurotransmission, in view of evidence for a preferential colocalization of A1 and A2A receptors in glutamatergic nerve terminals. By using in vivo microdialysis techniques, local perfusion of NMDA (3, 10 µm), the selective A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS 21680; 3, 10 µm), the selective A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 300, 1000 µm), or the non-selective A1-A2A receptor antagonist in vitro caffeine (300, 1000 µm) elicited significant increases in extracellular levels of dopamine in the shell of the nucleus accumbens (NAc). Significant glutamate release was also observed with local perfusion of CGS 21680, CPT and caffeine, but not NMDA. Co-perfusion with the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (APV; 100 µm) counteracted dopamine release induced by NMDA, CGS 21680, CPT and caffeine. Co-perfusion with the selective A2A receptor antagonist MSX-3 (1 µm) counteracted dopamine and glutamate release induced by CGS 21680, CPT and caffeine and did not modify dopamine release induced by NMDA. These results indicate that modulation of dopamine release in the shell of the NAc by A1 and A2A receptors is mostly secondary to their opposite modulatory role on glutamatergic neurotransmission and depends on stimulation of NMDA receptors. Furthermore, these results underscore the role of A1 vs. A2A receptor antagonism in the central effects of caffeine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.2004.02761.x
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  • 3
    Electronic Resource
    Electronic Resource
    Enabling role of adenosine A1 receptors in adenosine A2A receptor-mediated striatal expression of c-fos (2003)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 18 (2003), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: When striatal neurons are strongly activated they produce adenosine, which activates nearby adenosine A1 receptors (A1Rs) and adenosine A2A receptors (A2ARs). Although the effects of A1R or A2AR activation on neural activity in the striatum have been examined separately, the effects of coactivating both receptors has not been investigated. Using c-Fos immunohistochemistry as an indicator of neural activity, we examined the effects of coactivation of A1Rs and A2ARs on neural activity and their mechanism of interaction in the caudate-putamen, nucleus accumbens (NAc) and prefrontal cortex in rats. Administration of a motor-depressant dose of the A2AR agonist CGS 21680 (0.5 mg/kg i.p.) did not significantly induce c-fos expression in any of these brain regions. Administration of a motor-depressant dose of the A1R agonist CPA (0.3 mg/kg, i.p.) produced a small but significant induction of c-fos expression only in the shell of the NAc. Coadministration of CGS 21680 and CPA produced a synergistic induction of c-fos expression in the caudate-putamen, cingulate cortex, and especially the NAc. In the shell of the NAc administration of CPA significantly decreased extracellular dopamine levels measured by in vivo microdialysis and blocked CGS 21680-induced increases in dopamine levels. Because it has been previously shown that activation of dopamine D2 receptors (D2Rs) by endogenous dopamine blocks A2AR-mediated c-fos expression, it is hypothesized that the enabling role of A1Rs in A2AR-mediated striatal c-fos expression is related to the A1R-mediated inhibition of dopamine release.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2003.02747.x
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  • 4
    Electronic Resource
    Electronic Resource
    A multiple systems approach to drug abuse: implications for research and treatment (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Addiction 91 (1996), S. 0 
    Details
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1360-0443.1996.tb03591.x
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  • 5
    Electronic Resource
    Electronic Resource
    Nicotine and some related compounds: effects on schedule-controlled behaviour and discriminative properties in rats (1989)
    Springer
    Psychopharmacology 97 (1989), S. 295-302 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Nornicotine ; Cotinine ; Mecamylamine ; Stereoselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Behavioural effects of d- and l-nicotine, d- and l-nornicotine and l-cotinine were studied in two paradigms. In experiment 1, rats responded under a multiple fixed-interval (FI) 5 min, fixed-ratio (FR) 20 schedule of food presentation. Aside from differences in potency and time course, l-nicotine and the stereoisomers of nornicotine produced qualitatively similar effects on rates of responding. With increasing doses of drugs, FI response rates first increased and then decreased, while FR response rates only decreased. In contrast, d-nicotine did not significantly increase FI response rates at lower doses, and only decreased FI and FR response rates at higher doses. At doses up to 100 mg/kg, cotinine produced only dose-dependent increases in FI response rates and had no effect on FR response rates. Rate-increasing effects of cotinine were not blocked by mecamylamine. In experiment 2, rats were trained to discriminate between l-nicotine (0.1 mg/kg SC) and saline (0.1 mg/kg SC) in a two-bar, operant conditioning procedure under a tandem variable-interval (VI) 1 min, FR 10 schedule of food presentation. Full generalization was obtained to d-nicotine and to l- and d-nornicotine. Generalization to cotinine occurred only with large doses that contained significant amounts of nicotine present as an impurity. There was no generalization to non-nicotinic drugs (morphine and clenbuterol), even at doses that reduced response rates. The rank order of potency for nicotine and its analogues was similar in experiments 1 and 2: l-nicotine was 10–20 times more potent than d-nicotine and the stereoisomers of nornicotine (which did not show stereoselectivity in the rat). Cotinine was at least several hundred times less potent than nicotine. Behavioural potencies correlated with previously reported concentrations of the analogues needed to reduce binding of tritiated nicotine to rat brain membranes
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00439441
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  • 6
    Electronic Resource
    Electronic Resource
    Fixed-ratio schedules of oral ethanol self-administration in inbred mouse strains (1988)
    Springer
    Psychopharmacology 96 (1988), S. 431-436 
    Details
    ISSN: 1432-2072
    Keywords: Ethanol self-administration ; Operant behavior ; C57BL/6J mice ; BALB/cJ mice ; Fixed-ratio schedules ; Behavior genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies of ethanol reinforcement in BALB/cJ and C57BL/6J mice have shown that over a range of concentrations oral ethanol appeared to serve as a reinforcer only for the C57BL/6J mice. In the previous studies BALB/cJ mice maintained rates of responding for ethanol that only slightly exceeded the rates maintained by the vehicle, water. However, the quantity of ethanol consumed with the continuous reinforcement schedule (fixed ratio one) may have led to pharmacologically significant effects, given the high sensitivity to ethanol of this genotype. The present study tested whether and to what extent ethanol would maintain responding under increasing fixed ratio size in these two strains of mice at ethanol concentrations of 0%, 8%, and 16% (w/v). For the C57BL/6J mice, as fixed-ratio size increased from 1 to 2, 4, and 8, there were almost directly proportional increases in response rate at ethanol concentrations of 8% and 16% (w/v), but not at 0%. Post-session blood ethanol levels confirmed intake of pharmacologically significant quantities. The volume consumed per unit of body weight decreased as fixed-ratio size increased. For the BALB/cJ mice, at no condition did ethanol maintain responding at levels that significantly exceeded vehicle maintained responding. BALB/cJ mice did not differ from C57BL/6J mice as fixed-ratio size was increased during vehicle conditions. These results, along with earlier findings, demonstrate that ethanol can serve as a reinforcer for C57BL/6J mice but not in BALB/cJ mice over a range of schedule conditions. They further support the conclusion that genotype is an important determinant of ethanol reinforced behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02180019
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  • 7
    Electronic Resource
    Electronic Resource
    Opioid operant self-administration, analgesia, stimulation and respiratory depression inμ-deficient mice (1995)
    Springer
    Psychopharmacology 117 (1995), S. 23-31 
    Details
    ISSN: 1432-2072
    Keywords: Opioid ; Genetics ; Self-administration ; CXBK/ByJ ; Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is commonly thought thatμ-receptors play an important role in the reinforcing effects of opioids. In the present study, inbred strains widely divergent in CNS opiate receptor densities were used to investigate the influence of genetic variation in receptor concentration on opioid-reinforced behavior. In particular, the CXBK/ByJ mice were used as an investigative tool because of their significantly lower number of CNSμ opioid receptors. The behavioral pharmacology of opioids in theμ-deficient CXBK/ByJ mice was compared to other commonly used inbred mouse strains, C57BL/6J and BALB/cJ, and the opiate receptor rich CXBH/ByJ mice. Operant opioid reinforced behavior, opioid-induced locomotor stimulation, analgesia and respiratory depression were investigated in all four inbred strains. To assess the acquisition and maintenance of opioid reinforced behavior, oral self-administration of the potent benzimidazole opioid, etonitazene, was determined using an operant fixed-ratio schedule of reinforcement (FR 8). Acquisition of etonitazene-reinforced behavior was established in all four strains including theμ-deficient CXBK/ByJ mice. However, there were significant genetic differences in the amount of drug intake during the maintenance of opioid-reinforced behavior and extinction behavior following vehicle substitution. For example, drug intake was significantly greater in the BK versus BH mice during the maintenance phase and an extinction burst was seen in the BH but not the BK mice following vehicle substitution. Thus,μ-receptor density may not account for individual variability in the acquisition of opioid-reinforced behavior under these conditions. Sensitivity to etonitazene-induced respiratory depression, stimulation of locomotor activity and analgesia were unrelated to drug intake during self-administration sessions across these four inbred strains. These data indicate that inherited differences in CNSμ-opiate receptor concentrations do not affect acquisition of etonitazene-reinforced behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245094
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  • 8
    Electronic Resource
    Electronic Resource
    Differences in morphine reinforcement property in two inbred rat strains: associations with cortical receptors, behavioral activity, analgesia and the cataleptic effects of morphine (1993)
    Springer
    Psychopharmacology 112 (1993), S. 183-188 
    Details
    ISSN: 1432-2072
    Keywords: Morphine ; Behavioral activity ; Analgesia ; Rat ; Self-administration ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the current study was to investigate genetic differences between two inbred strains of rats, Fisher-344 (F344/N) and Wistar Albino Glaxo (WAG/GSto), in a number of drug-naive and drug-related behaviors, including oral and intravenous morphine self-administration. F344/N and WAG/GSto rats differed in drug-naive behaviors such as nociception, rearing and sensitivity to lick suppression tests but did not differ in locomotor activity, ambulation or grooming behavior. F344/N rats were less sensitive to thermal stimuli as measured via tail-flick response, and more sensitive to the suppressive effects of intermittent shock in a lick suppression test. The F344/N rats demonstrated a significantly greater amount of rearing in open field tests but did not differ from WAG/GSto rats in locomotor activity, ambulation or grooming behavior. In addition to the behavioral results, naive F344/N and WAG/GSto rats were found to differ in μ and α2 receptor concentrations (F344/N〉WAG/GSto) and in 5HT2 and D2 affinity constants (WAG/GSto〉F344/N). These two inbred rat strains also differed in drug-related behaviors. F344/N rats showed significantly greater depression of locomotor activity at morphine 3 mg/kg than WAG/GSto rats. In addition, F344/N rats consumed significantly greater amounts of morphine in a two-bottle choice procedure and morphine maintained significantly greater amounts of behavior during intravenous self-administration sessions. Importantly, drug maintained behavior was significantly greater than with vehicle only in the F344/N rats during operant self-administration sessions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244908
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  • 9
    Electronic Resource
    Electronic Resource
    Inbred rat strain comparisons indicate different sites of action for cocaine and amphetamine locomotor stimulant effects (1991)
    Springer
    Psychopharmacology 104 (1991), S. 457-462 
    Details
    ISSN: 1432-2072
    Keywords: Locomotor Activity ; Cocaine ; Amphetamine ; Behavior genetics ; Rats ; Dopaminergic D1 ; Dopaminergic D2 ; Dopamine uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cocaine and amphetamine produce several behavioral effects, most notably locomotor stimulation. Biochemically, evidence suggests specific involvement of dopaminergic systems, although not necessarily identical sites, in mediating cocaine- and amphetamine-induced locomotor stimulation. This study examined the effects of cocaine or amphetamine on locomotor activity in rats from the ACI, F344, LEW and NBR inbred strains. Dose-dependent increases in locomotor activity were found for both drugs in all strains. However, large potency and efficacy differences were found. Further, significant strain by drug interactions were found, in that the strain rank order for stimulant response to the two drugs was not identical. Since striatal dopaminergic neurons influence locomotor activity, we also assessed ligand affinity and receptor density of dopamine transporters and dopaminergic D1 and D2 receptors in striatal tissue from these same strains of rats. No differences in these receptor binding parameters were found. These findings support the conclusion that these two drugs produce their locomotor stimulant effects through different sites of action, and that genetic differences in response to these drugs at the behavioral level do not appear to be mediated significantly by differences in structure or number of striatal dopaminergic sites. The further use of genetic methods, however, may aid in determining the specific sites of action of these widely used stimulant drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245649
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  • 10
    Electronic Resource
    Electronic Resource
    Behavior maintained under second-order schedules of intravenous morphine injection in squirrel and rhesus monkeys (1977)
    Springer
    Psychopharmacology 51 (1977), S. 235-242 
    Details
    ISSN: 1432-2072
    Keywords: Morphine ; Second-order schedules ; Drug-seeking behavior ; Self-administration ; Squirrel monkeys ; Rhesus monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Under second-order schedules of morphine injection, high rates of responding by squirrel and rhesus monkeys were maintained when morphine was injected intravenously only at the end of each session. Every 30th key-pressing response during a 60-min interval produced a 2-s light; the first 30-response component completed after 60 min produced both the light and intravenous injection of morphine. A mean rate of approximately one response per second was maintained by doses of morphine ranging from 0.75–1.5 mg/kg. A pause in responding after each light presentation was followed by rapid responding until the light was produced again; pauses became shorter as the 60-min interval progressed. When brief light presentations were omitted, but morphine was still injected, response rates decreased and patterns of responding were altered. When saline injections were substituted for morphine injections, but the brief light was still presented, responding decreased markedly within three to five sessions and patterns of responding were altered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431630
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