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  • 1
    Electronic Resource
    Electronic Resource
    Acute and subchronic effects of neuroleptics on quantitative measures of discriminative motor control in rats (1984)
    Springer
    Psychopharmacology 84 (1984), S. 368-373 
    Details
    ISSN: 1432-2072
    Keywords: Motor control ; Haloperidol ; Chlorpromazine ; Clozapine ; Neuroleptics ; Chlordiazepoxide ; Force band ; Force variance ; Tremor ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Operant-conditioning methods were used to train rats to reach through an opening in an operant chamber to exert forces on a silent, neraly isometric force-sensing manipulandum. The reinforcement contingency required the rat to hold forelimb force at 20–50 g for a minimum of 2 s. Once established, this ‘hold-in-the-band’ behavior yielded three measures of performance (time on task, number of reinforcers, variance of in-band force). Variance of in-band force was presumed to reflect steadiness of forelimb control. Acute drug effects on the three dependent variables were assessed for dose ranges of haloperidol (HAL), chlorpromazine (CPZ), clozapine (CLZ), and chlordiazepoxide (CDP). Moreover, the effects of HAL (0.5 mg/kg) and CLZ (5.0 mg/kg) were examined in a subchronic (28 day) dosing regimen. The acutely administered neuroleptics (HAL, CPZ, CLZ) produced dose-related decreases in time on task and number of reinforcers, but did not significantly affect variance of in-band force. The subchronic paradigm produced similar results. CDP did not significantly affect variance of in-band force and the 5.0 mg/kg dose produced a slight, but non-significant increase in time on task while significantly decreasing number of reinforcers; a trend opposite to that seen for the neuroleptics, which produced parallel effects on these two measures. The results suggest that the neuroleptics impaired performance by affecting the tendency to initiate responding instead of affecting the capacity to maintain steady forelimb force once a response was started.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00555215
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of pimozide, across doses and within sessions, on discriminated lever release performance in rats (1988)
    Springer
    Psychopharmacology 96 (1988), S. 21-28 
    Details
    ISSN: 1432-2072
    Keywords: Pimozide ; Neuroleptics ; Reaction time ; Response initiation ; Dopamine ; Operant behavior ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract By using either water or food reinforcement, rats were trained to perform a discriminated lever release task (DLR), which required the rat to hold an operant lever in the closed position through one of five randomly presented foreperiods (2–6 s) and to release the lever within 0.5 s of the onset of a light discriminative stimulus. The procedure is analogous to the method used in human reaction time studies, except that here the procedure was free-operant, not fixed-trial. The effects of pimozide (0.12, 0.25, and 0.50 mg/kg) on this behavior were evaluated in terms of numbers of total responses, reinforced responses (successful releases), anticipatory responses, and extended responses (holding too long). Significant dose-dependent decreases in total responses and in reinforced responses were seen as supporting the hypothesis of a deficit in response initiation, which is often invoked to account for neuroleptic-induced reductions in discriminated active avoidance. Pimozide also increased the proportion of extended responses, suggesting that the drug affected the nature of responding as well as the tendency to respond. In the DLR task, pimozide produced substantial within-session decrements in both total responses and number of reinforced responses; however, extended responses exhibited within-session increases at the lowest dose. The results were discussed from both behavioral and pharmacological perspectives. The former emphasized motor effects and response initiation deficits, while the latter jointly considered neuronal responses to neuroleptic challenge and the dopamine release that results from behavioral activity itself.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431528
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  • 3
    Electronic Resource
    Electronic Resource
    Unlike haloperidol, clozapine slows and dampens rats' forelimb force oscillations and decreases force output in a press-while-licking behavioral task (1994)
    Springer
    Psychopharmacology 116 (1994), S. 19-25 
    Details
    ISSN: 1432-2072
    Keywords: Haloperidol ; Clozapine ; Neuroleptics ; Tremor ; Response force ; Power spectra ; Forelimb ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to detect putative differences in the behavioral effects of clozapine and haloperidol, rats were trained to use a single forelimb to exert continuous pressure on a force-sensing operandum. Behavior was maintained by presenting a water-filled dipper for consumption only as long as the force remained above a specified level (the water fountain task). Effects of clozapine (2.0, 4.0, 8.0 mg/kg) and haloperidol (0.02, 0.04, 0.08, 0.12 mg/kg) on the forelimb force oscillations manifested during the operandum pressing episodes were analyzed with power spectral analysis and other quantitative methods. All rats exhibited force oscillations with a fundamental frequency near 7 Hz. Clozapine shifted the frequency to lower values (i.e., oscillation slowing), while haloperidol shifted oscillations to slightly higher frequencies. Moreover, clozapine reduced power in the region of the spectrum above 5 Hz. In contrast, haloperidol tended to increase power in these regions. Time domain analyses of the force-time waveforms indicated that haloperidol increased force emission during the hold phase of the forelimb response, and clozapine decreased this measure. The results are congruent with the high extrapyramidal side effects of haloperidol and the lack of such effects of clozapine in the clinic. In addition, clozapine may have antitremor effects in rats as it does in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244866
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  • 4
    Electronic Resource
    Electronic Resource
    Microcatalepsy and disruption of forelimb usage during operant behavior: differences between dopamine D1 (SCH-23390) and D2 (raclopride) antagonists (1994)
    Springer
    Psychopharmacology 115 (1994), S. 24-30 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Neuroleptics ; SCH-23390 ; Raclopride ; Response duration ; Catalepsy ; Operant behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an experiment designed to distinguish between the behavioral consequences of treatment with SCH-23390, a D1 dopamine receptor blocker, and raclopride, a D2 antagonist, rats were trained to perform a water-reinforced forelimb operant response. Response rate and the duration of each forelimb contact with the operandum were recorded. In addition, the durations of the rat's visits to the reward well were detected by a photobeam which was blocked by the rat's muzzle as it remained at the reward well. In a between-groups dosing design, separate groups of rats (11–13 rats/group) received SCH-23390 (0, 0.01, 0.02, 0.04, 0.08, 0.12 mg/kg, IP, 30 min) or raclopride (0. 0.05, 0.1, 0.2, 0.4, 0.8 mg/kg, IP, 30 min) for 21 consecutive days. Quantitative analyses indicated that for comparable amounts of operant rate reduction, raclopride had a significantly greater tendency than SCH-23390 to increase the duration of operant responses and to increase the maximum muzzle entry duration (i.e., to induce microcatalepsy). The results support the idea that at relatively low doses D2 antagonism is more likely than D1 antagonism to produce effects identified preclinically with extrapyramidal side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244747
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  • 5
    Electronic Resource
    Electronic Resource
    Chronic haloperidol produces a time- and dose-related slowing of lick rhythm in rats: implications for rodent models of tardive dyskinesia and neuroleptic-induced parkinsonism (1998)
    Springer
    Psychopharmacology 137 (1998), S. 50-60 
    Details
    ISSN: 1432-2072
    Keywords: Key words Haloperidol ; Scopolamine ; Trihexyphenidyl ; Quipazine ; Ritanserin ; Tongue ; Licking ; Lick rhythm ; Lick force ; Neuroleptics ; Tardive dyskinesia ; Parkinsonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to characterize the development of orolingual motor effects of chronic haloperidol treatment in rats, this typical neuroleptic was administered for 102 days while daily measurements of tongue movement dynamics (peak force, lick rhythm, number of licks) during water licking were recorded. After chronic haloperidol dosing (vehicle, 0.06. 0.12, 0.24 mg/kg for four separate groups) for 32 days and continuing every second or third day of the chronic dosing period, the effects of cholinergic (scopolamine: 0.05–0.20 mg/kg; trihexyphenidyl: 0.15–1.0 mg/kg) or serotonergic (ritanserin: 0.5–4.0 mg/kg; quipazine: 0.5–4.0 mg/kg) probe drugs were examined for their capacity to antagonize the alterations in licking behavior induced by haloperidol. Haloperidol dose-dependently reduced peak force and number of licks, effects which were apparent within 2 or 3 days of the start of treatment. Significant effects of haloperidol on lick rhythm first emerged on day 13 and gradually increased in magnitude through the remaining treatment period. Scopolamine, trihexyphenidyl, and quipazine reduced haloperidol’s effects on at least one measure of licking behavior. During a 7-day haloperidol withdrawal period, the four dosage groups were similar on all measures of tongue dynamics. Overall, the results exhibited features suggesting the co-occurrence of Parkinson-like and tardive dyskinesia-like effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050592
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  • 6
    Electronic Resource
    Electronic Resource
    Raclopride, but not SCH 23390, induces maldirected jumping in rats trained to perform a run-climb-run behavioral task (1993)
    Springer
    Psychopharmacology 112 (1993), S. 518-520 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Neuroleptics ; SCH 23 390 ; Raclopride ; Jumping ; Learned behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to explore further the putative differential behavioral consequences of D1 dopamine and D2 dopamine receptor antagonism, SCH 23 390 (0.01–0.12 mg/kg) and raclopride (0.12–1.0 mg/kg) were administered to two separate groups of rats that had been trained in an eight-trial-per-day format to run down an alleyway, climb a vertical rope, and run across a horizontal board to access sweetened milk. Although both drugs dose-dependently reduced the speed of task completion, only raclopride produced vigorous, maldirected jumping behavior in the floor segment of the apparatus. The number of such jumps increased with dose. This raclopride-specific jumping phenomenon may provide a new behavioral arena for investigating the functional differences between D1 and D2 receptor antagonism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244903
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  • 7
    Electronic Resource
    Electronic Resource
    Subchronic effects of clozapine and haloperidol on rats’ forelimb force and duration during a press-while-licking task (1997)
    Springer
    Psychopharmacology 130 (1997), S. 249-253 
    Details
    ISSN: 1432-2072
    Keywords: Key words Clozapine ; Haloperidol ; Subchronic ; Tolerance ; Forelimb ; Force ; Tremor ; Neuroleptics ; Atypical ; Antipsychotic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to compare and contrast the behavioral effects of the typical neuroleptic haloperidol with the atypical neuroleptic clozapine, ten daily doses of these drugs were administered to separate groups of rats trained to extend the forelimb through a rectangular hole and to exert downward pressure on a force transducer to gain access to water. Doses were individually titrated daily for each rat in an attempt to achieve a 50% reduction in time on task (analogous to response rate) during 8-min daily sessions. Clozapine-treated rats exhibited dramatic tolerance to the drug’s suppressive effect on time on task. In contrast, haloperidol rats displayed little tolerance on this measure. Despite the tolerance reflected by time on task, no tolerance was seen in clozapine’s marked slowing of the dominant frequency of oscillations in forelimb force as measured by Fourier analysis of the force-time recordings. Haloperidol did not slow the dominant frequency. No tolerance was seen for clozapine’s effects on forelimb force or tremor measures. Haloperidol did not significantly affect forelimb force. Both haloperidol and clozapine produced increases in the duration of long-duration forelimb responses, and no tolerance was seen for either drug on this measure of behavior. For clozapine, the dissociation between the tendency to respond (time on task) and the observed slowing of the dominant frequency may reflect effects peculiar to atypical neuroleptics, while the lengthening of long-duration responses by both drugs may reflect a more general behavioral effect that is characteristic of both typical and atypical antipsychotic drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050236
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