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  • 1
    Electronic Resource
    Electronic Resource
    The effect of MK-801 and other antagonists of NMDA-type glutamate receptors on brain-stimulation reward (1989)
    Springer
    Psychopharmacology 99 (1989), S. 87-90 
    Details
    ISSN: 1432-2072
    Keywords: Glutamate ; Kainate ; Ketamine ; Kynurenic acid ; MK-801 ; NMDA ; Phencyclidine ; Rat ; Self-stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract MK-801 is a ligand at phencyclidine recognition sites associated with NMDA-coupled cation channels, where it acts as a potent noncompetitive antagonist of central glutamate/aspartate (NMDA-type) receptors. Low doses (10–100 μg/kg IP) produced a dose-related and prolonged (〉1 h) enhancement of variable-interval self-stimulation responding. Higher doses (300 μg/kg) caused flaccid ataxia and disrupted responding. Ketamine HCl (3.0–100 mg/kg IP), a dissociative anaesthetic binding to the phencyclidine site, produced a similar response pattern, but facilitation was less prolonged and occurred over a narrower dose range. Kynurenic acid (3.0–300 mg/kg IP), a nonselective competitive antagonist of glutamate receptors, produced only depression of responding, possibly the result of kynurenate-induced blockade of central kainate and/or quisqualate receptors. The behavioural stimulant effects of MK-801 appear to be an intrinsic and essential feature of selective NMDA antagonists, and these effects of MK-801 differ qualitatively and quantitatively from the well-known facilitatory effects of dopamine-dependent stimulants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00634458
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  • 2
    Electronic Resource
    Electronic Resource
    Midazolam cue in rats: Generalization tests with anxiolytic and other drugs (1985)
    Springer
    Psychopharmacology 87 (1985), S. 233-237 
    Details
    ISSN: 1432-2072
    Keywords: Midazolam ; Benzodiazepines ; Pentobarbitone ; Drug discrimination ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Some characteristics of the discriminative stimulus (cue) effects of midazolam, a short-acting benzodiazepine, have been determined in rats. A standard two-bar operant conditioning procedure with food reinforcers delivered on a tandem schedule was used. The 0.4 mg/kg dose of midazolam used for training was well discriminated, typically yielding at least 95% correct responding. Other benzodiazepines increased the percentage of drug-appropriate responding in a dose-related manner and were generalized at doses which had little effect on the overall rate of responding. Doses of pentobarbitone which greatly reduced the overall rate of responding were also generalized with midazolam. Amphetamine, oxotremorine, picrotoxin, morphine, nicotine, quipazine and Ro 15-1788 were not generalized, even at doses which severely suppressed overall response rates. The midazolam cue possesses a considerable degree of specificity and provides a potentially useful assay for drug action at the benzodiazepine receptor complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431814
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  • 3
    Electronic Resource
    Electronic Resource
    Nitric oxide synthesis, epileptic seizures and kindling (1995)
    Springer
    Psychopharmacology 119 (1995), S. 115-123 
    Details
    ISSN: 1432-2072
    Keywords: Epilepsy ; Kindling ; l-Arginine ; l-NAME ; l-Nitro-arginine ; LTP ; Nitric oxide ; Seizures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nitric oxide (NO) has been implicated in synaptic changes underlying long-term potentiation and some forms of learning. It is unclear, however, whether NO contributes to long-term changes associated with the kindling of epileptic seizures. In the present study rats were treated, on the first 6 days of kindling, withl-arginine (l-Arg), the endogenous donor from which NO derives, or withl-nitro-arginine (l-No-Arg), a competitive inhibitor of NO synthesis, or with vehicle. Drugs were given in doses previously shown to affect learning or other behaviour.l-Arg (750 mg/kg IP) did not affect kindling or seizure severity.l-No-Arg (100 mg/kg) prolonged the duration of afterdischarges and convulsions on treatment days but did not advance kindling or affect seizures on subsequent days. A second experiment examined the possible rôle of NO in the development of resistance to seizures following prior seizures. Six or more stimuli were administered at 10-min intervals to fully-kindled rats after injection ofl-No-Arg or vehicle. Vehicle-treated rats became progressively more resistant to afterdischarges and convulsions with successive stimulations butl-No-Arg-treated rats failed to do so. Rats injected withl-No-Arg also showed an unexpected high mortality in the ensuing 24 h.l-No-Arg appeared to have no direct effect on the course of kindling but impaired the development of postictal resistance, and increased the duration and lethal after-effects of closely repeated seizures. The results do not support suggestions that antagonists of NO might prove clinically useful as anticonvulsants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246062
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of intracerebroventricular and systemic injections of caerulein, a CCK analogue, on electrical self-stimulation and its interaction with the CCKA receptor antagonist, L-364,718 (MK-329) (1990)
    Springer
    Psychopharmacology 101 (1990), S. 384-389 
    Details
    ISSN: 1432-2072
    Keywords: Caerulein ; Cholecystokinin ; L-364,718 ; CCKA receptors ; Self-stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Systemic administration of caerulein (10–100 µg/kg SC), a potent analogue of cholecystokinin, caused a profound dose-related depression of variable-interval self-stimulation, followed by progressive recovery within 60 min. Intracerebroventricular injection of caerulein (3–1000 ng) was not more effective than systemic injection, while injections into the nucleus accumbens (3–100 ng bilaterally) were without detectable effect. Systemic injections of L-364,718 (70–700 µg/kg IP), a specific competitive antagonist of CCKA (“peripheral-type”) receptors, had no effect on self-stimulation when given alone. When given in combination with caerulein, L-364,718 (200 µg/kg IP) significantly reduced the inhibitory effect of caerulein (30 µg/kg SC); however, this dose, and higher doses of L-364,718, failed to confer complete protection. It is concluded that self-stimulation performance may be subject to modulation by CCK receptors distributed predominantly in the peripheral nervous system and that some but not all of these receptors are CCKA receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244058
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Midazolam cue in rats: Effects of Ro 15-1788 and picrotoxin (1986)
    Springer
    Psychopharmacology 89 (1986), S. 183-188 
    Details
    ISSN: 1432-2072
    Keywords: Midazolam ; Benzodiazepines ; Pentobarbitone ; Ro 15-1788 ; Picrotoxin ; Nicotine ; Drug discrimination ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus effect of midazolam, a short-acting benzodiazepine, was used for testing the effects of drugs thought to act as antagonists at different sites in the proposed benzodiazepine receptor complex. Rats were trained in a standard two-bar operant conditioning procedure with food reinforcers delivered on a tandem schedule. The 0.4 mg/kg dose of midazolam used for training was well discriminated, typically yielding at least 95% correct responding. The benzodiazepine receptor antagonist Ro 15-1788 blocked the discriminative effect of midazolam but did not influence generalization to pentobarbitone (7.5 mg/kg). The indirect GABA antagonist picrotoxin attenuated both generalization to pentobarbitone and its response rate-reducing effect. Picrotoxin had no effect on the discriminative effect of midazolam at 0.4 mg/kg but it blocked the effect of 01 mg/kg. Even in doses which reduced overall response rates, nicotine did not block discrimination of midazolam (0.4 mg/kg). The results are consistent with models which postulate a GABA-linked ion channel which is a site of action for barbiturates and which is “downstream” of the benzodiazepine receptor itself.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00310626
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  • 6
    Electronic Resource
    Electronic Resource
    5-HT1A agonists and dopamine: the effects of 8-OH-DPAT and buspirone on brain-stimulation reward (1991)
    Springer
    Journal of neural transmission 83 (1991), S. 139-148 
    Details
    ISSN: 1435-1463
    Keywords: Buspirone ; dopamine ; feeding ; presynaptic receptor ; self-stimulation ; 5HT1A receptor ; 8-OH-DPAT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two specific 5-HT1A agonists, 8-OH-DPAT (0–300 Μg/kg), and buspirone (0–3.0 mg/kg), were tested on variable-interval, threshold-current self-stimulation of rat lateral hypothalamus. Buspirone produced a prolonged monotonic depression of responding, whereas the effects of 8-OH-DPAT were biphasic: 3.0 Μg/kg produced a sustained enhancement of responding while higher doses (100–300 Μg/kg) produced a relatively short-lasting depression. This biphasic pattern parallels previously reported effects of 8-OH-DPAT on food intake and on various other behaviours. Threshold-current self-stimulation is highly sensitive to alterations in dopaminergic transmission but relatively insensitive to changes in 5-HT. Thus the facilitatory effect of low-dose 8-OH-DPAT seems most plausibly interpreted in terms of enhanced dopaminergic transmission. This could be brought about by 5HT1A autoreceptor-mediated inhibition of 5-HT release and consequent disinhibition of dopaminergic transmission. Depression of self-stimulation by higher doses of 8-OH-DPAT may reflect the activity of 8-OH-DPAT at postsynaptic 5-HT receptors, with consequent inhibition of DA transmission. Suppression of responding after buspirone at all doses tested may reflect the action of this compound as a partial agonist at postsynaptic 5-HT receptors, and/or its effects on other systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01244460
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  • 7
    Electronic Resource
    Electronic Resource
    The effect of a 5-HT3 receptor antagonist, ondansetron, on brain stimulation reward, and its interaction with direct and indirect stimulants of central dopaminergic transmission (1993)
    Springer
    Journal of neural transmission 91 (1993), S. 1-11 
    Details
    ISSN: 1435-1463
    Keywords: d-Amphetamine ; dopamine ; nicotine ; ondansetron ; 5-HT3 receptor ; self-stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 5-HT3 receptors are abundant in central dopamine (DA) terminal areas. They do not affect basal DA turnover but appear to modulate DA release by e.g. morphine and nicotine. The interpretation of these findings is uncertain, and it is unclear whether 5-HT3 receptors also influence the activity of compounds such as amphetamine and cocaine, which act more directly on the DA synapse. Variable-interval (VI), threshold-current hypothalamic self-stimulation can provide a continuous index of central dopaminergic activity, but is relatively insensitive to changes in 5-HT and thus offers a means of investigating this question. In the present study, a selective 5-HT3 receptor antagonist, ondansetron (GR 38032F) (1.0 to 1000 μg/kg sc), had no effect on VI self-stimulation, nor did a 100 μg/kg dose affect facilitation of responding byd-amphetamine (500 jig/kg ip). Ondansetron (100 μg/kg) reduced the initial depression of self-stimulation by high-dose nicotine (400 μg/kg), but not the ensuing facilitation. Similar results were obtained in rats “sensitized” to nicotine by prior chronic exposure. These results support the proposal that 5-HT3 receptors, normally quiescent under basal conditions, mediate the excitatory effect of compounds acting upstream from the DA neuron, such as nicotine, but do not affect the dopaminergic synapse directly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01244914
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