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  • Idazoxan  (3)
  • Self-stimulation  (3)
  • 1
    ISSN: 1432-2072
    Keywords: Chlordiazepoxide ; Self-stimulation ; Selfregulated duration ; Response duration ; Reinforcement ; Fixed interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were exposed to a fixed-interval 60-s schedule under which responding was maintained by electrical stimulation of the lateral hypothalamus. The duration of stimulation was controlled by the duration of each lever press that initiated reinforcement. The effects of variation in current intensity and administration of several chlordiazepoxide (CDP) doses (2.5–20 mg/kg IP) were investigated. The duration of stimulation was inversely related to current intensity. Administration of CDP resulted in increases in response rate and the durations of reinforced and nonreinforced responses. CDP increased the response duration reliably more with non-reinforced responses than with responses that served to regulate the duration of stimulation. Thus CDP-induced increases in the duration of brain stimulation with the single lever self-regulation procedure may not be attributed to a specific effect of this compound on neural processes underlying reinforcement. The present results indicate the utility of intermittent schedules in establishing the specificity of drug effects on self-regulated duration of brain stimulation in the single-lever condition.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 95 (1988), S. 413-417 
    ISSN: 1432-2072
    Keywords: DRL-schedule ; Imipramine ; Mianserin ; Idazoxan ; Yohimbine ; Amphetamine ; α2-Adrenoceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have reported that antidepressant drugs exert specific effects on responding maintained by DRL schedules of reinforcement, giving rise to increased frequencies of reinforcement. In order to investigate whether the α2-adrenoceptor antagonist idazoxan would produce similar effects, the actions of this compound were compared with those of yohimbine, imipramine, mianserin and d-amphetamine in rats trained to lever press for food reinforcement on a DRL 60-s schedule. Neither imipramine nor mianserin produced any effects on response rate or reinforcement frequency, except at the highest doses. In contrast, both idazoxan and yohimbine gave rise to dose-related increases in rates of responding and consequent decreases in reinforcement frequencies. Amphetamine also increased responding, but higher doses of this drug produced marked hyperactivity and stereotyped movements which were not observed after idazoxan and yohimbine. Although the present behavioural baseline was not sensitive to antidepressants, it demonstrated an unexpected activity of two α2-adrenoceptor antagonists which deserves further investigation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 96 (1988), S. 243-249 
    ISSN: 1432-2072
    Keywords: FI-schedule ; Drug discrimination ; Idazoxan ; Yohimbine ; d-Amphetamine ; Noradrenaline ; α2-Adrenoceptors ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although yohimbine has long been known to increase arousal, reactivity and anxiety in animals and humans, little is known about the behavioural effects of more selective α2-adrenoceptor antagonists such as idazoxan. In a recent experiment, however, it was found that in rats both yohimbine and idazoxan increased low rates of lever pressing, an effect also produced by amphetamine. The purpose of the present study was to investigate further the effects of yohimbine and idazoxan in comparison with those of d-amphetamine on the operant behaviour of rats. In rats trained to press a lever on a FI 60s schedule to obtain food both yohimbine and idazoxan increased response rates, although the effect of yohimbine was considerably greater than that of idazoxan. Lower doses of d-amphetamine had no consistent effect on overall rates of responding whereas a higher dose suppressed responding. Characteristically, d-amphetamine increased responding during early portions of the intervals and decreased responding during the final portions. Idazoxan and yohimbine tended to increase responding throughout the intervals except immediately after reinforcement. When idazoxan was administered in combination with prazosin FI response rates were markedly decreased. Administration of DSP4 did not alter the response rate-increasing effects of either yohimbine or idazoxan. In rats trained to discriminate d-amphetamine from saline both idazoxan and yohimbine gave rise to responding on the saline associated lever. Combination of idazoxan with d-amphetamine did not antagonise the amphetamine cue but produced substantial reductions in response rates, probably due to toxicity. These results confirm previous findings that both idazoxan and yohimbine have behavioural stimulant effects but do not clarify the mechanisms involved. It is clear, however, that the behavioural actions of these α2-adrenoceptor antagonists have little in common with those of the psychomotor stimulant amphetamine.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 99 (1989), S. 117-121 
    ISSN: 1432-2072
    Keywords: Idazoxan ; Drug discrimination ; Yohimbine ; Buspirone ; α2-Adrenoceptors ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate a dose of the α2-adrenoceptor antagonist idazoxan (10 mg/kg IP) from saline. The discriminative stimulus produced by idazoxan was dose related and generalised to yohimbine. However, generalisation did not occur with a variety of compounds from other pharmacological categories including the α1-adrenoceptor agonist cirazoline, the α2-adrenoceptor antagonist prazosin, and the α2-adrenoceptor agonist clonidine. The idazoxan stimulus was not antagonised by either prazosin or clonidine, although it was clear that idazoxan antagonised the reductions in response rate produced by clonidine. Dose-related responding on the idazoxan-associated lever was produced by the anxiolytics buspirone and ipsapirone and by their metabolite MJ 13653 (1-PP), which has previously been shown to be an α2-adrenoceptor antagonist. In general, however, high levels of generalisation occurred with these three compounds only at doses which substantially reduced response rates. These results demonstrate that idazoxan can give rise to a discriminative stimulus which is probably mediated through antagonism at α2-adrenoceptors although the failure of clonidine to block the idazoxan stimulus is difficult to explain.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Key words 7-OH-DPAT ; d-Amphetamine ; Dopamine ; Extinction ; Haloperidol ; Progressive-ratio ; Rat ; Self-stimulation ; Ventral tegmental area
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Progressive-ratio (PR) schedules, which have been widely used to study the reinforcing efficacy of various reinforcers (in particular IV psychostimulants), have been very seldom applied to the study of positively reinforcing electrical brain stimulation (EBS). In the present study, rats were required to emit a progressively increasing number of lever-presses (3,4,6,7,9,11,14,16, etc.) for access to successive reinforcers (periods of VTA self-stimulation). Each period of self-stimulation consisted of ten trains of square pulses of EBS; each train was available under a continuous reinforcement schedule. The number of periods of EBS earned during a session was deemed the breaking point (BP). After acquisition and stabilization of self-stimulation, a study was carried out to verify that changes in the strength of the EBS (i.e. changes in the frequency, the intensity or the pulse duration, one parameter at a time) induced changes in the BP. The effects of IP pretreatments with d-amphetamine, the dopamine D3/D2 receptor agonist 7-OH-DPAT and haloperidol were then assessed. Decreases in the strength of EBS decreased the BP. However, increasing the strength above training values resulted in minimal increases in the BP. d-Amphetamine (0.25–1 mg/kg) dose-dependently increased the BP; additionally, when the reinforcer was withheld (i.e. in conditions of extinction, with the stimulator turned off) d-amphetamine was also found to augment the BP. This might indicate that d-amphetamine preferentially potentiated the motivational (non-rewarded presses) aspects of VTA self-stimulation under this type of PR schedule. 7-OH-DPAT had biphasic effects: at low doses (0.01 and 0.03 mg/kg), it tended to decrease the BP while higher doses (1 and 3 mg/kg) robustly increased the BP. Under conditions of extinction, 7-OH-DPAT (1 mg/kg) had a tendency to increase the BP, but this effect was not statistically significant and did not approach the magnitude of effects observed with d-amphetamine. Haloperidol (0.08–0.48 mg/kg IP) dose-dependently reduced the BP, suggestive of a decrease in the reinforcing efficacy of the EBS. These results show that rats can be trained to self-administer EBS of the VTA under a PR schedule of reinforcement and that this behaviour is sensitive to disruption or potentiation of dopaminergic neurotransmission.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: 7-OH-DPAT ; Apomorphine ; Dopamine ; D3 receptors ; Locomotor activity ; Progressive-ratio ; Quinpirole ; Rat ; Self-stimulation ; Stereotypies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assessed the effects of IP injections of (±) 7-hydroxy-2(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine agonist that has been reported to have preferential affinity for the dopamine D3 subtype of receptor, on four behavioural procedures in the rat: 1) spontaneous locomotion, 2) electrical self-stimulation of the ventral tegmental area (VTA), using the curve-shift procedure 3) operant responding for food under a progressive-ratio (PR) schedule and 4) induction of stereotypies. The effects of (±) 7-OH-DPAT were compared to the effects of apomorphine, a non-specific DA agonist, and quinpirole, a selective D2/D3 agonist. All three dopamine agonists decreased locomotor activity at low doses (0.01–0.3 mg/kg), and only apomorphine had clear locomotor stimulant effects at the highest dose tested (3 mg/kg). The three drugs dose-dependently depressed VTA self-stimulation in a similar way, with low doses inducing a fairly parallel rightward shift of the frequency/rate curves and higher doses flattening the curves. In contrast, responding for food under the PR schedule appeared to be differentially affected by the three agonists: 7-OH-DPAT induced a biphasic effect, with a maximal decrease in lever-pressing at 0.1 mg/kg, followed by a return to baseline levels with increasing doses (0.3–3 mg/kg); quinpirole showed a tendency to decrease responding over the whole dose-range tested with a maximal effect of about 50% of baseline between 0.25 and 1 mg/kg, and apomorphine dose-dependently decreased responding, with rats ceasing to respond at 0.3 mg/kg. All three DA agonists induced stereotypies, but there was a difference in the maximal stereotypy score induced by each of the ligands: 7-OH-DPAT produced a lower maximal effect than quinpirole or apomorphine. This indicates that each of the three dopamine agonists preferentially induced different types of stereotypies. Together, these data suggest that the putative dopamine D3 agonist 7-OH-DPAT, at low doses, has depressant effects similar to those induced by low doses of the other two DA agonists. Differences in the behavioural effects of higher doses were, however, mostly observed in two procedures, PR responding and induction of stereotypies.
    Type of Medium: Electronic Resource
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