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Methylphenidate hydrochloride (ritalin) reduces operant responding in rats by affecting the spatial and temporal distributions of responses.

Methylphenidate hydrochloride (Ritalin[R]) is a psychomotor stimulant that is the drug of choice in the pharmacological treatment of Attention Deficit Disorder (for recent reviews, see Gittelman Klein & Abikoff, 1989; Solanto, 1986) and narcolepsy (Franz, 1985).

Many behavioral effects of drugs are rate dependent (Branch, 1984; Dews, 1955, 1958; Dews & Wenger, 1977; Lyon & Robbins, 1975; Robbins, Jones, & Sahakian, 1989; Sanger & Blackman, 1976). The rate-dependency principle states that the behavioral effects of psychomotor stimulants are inversely related to the frequency of behavior under control conditions: Low-rate operant behavior tends to increase, whereas high-rate operant behavior tends to decrease. The rate-dependency principle holds across a wide range of procedures, species, and stimulants, methylphenidate included (Dews, 1958; Robbins et al., 1989; Sagvolden, Jenssen, & Brorson, 1983; Sanger & Blackman, 1976).

Operant behavior might be described in terms of a class of responses defined by its consequences (the descriptive operant response class, e.g., lever presses of at least 15g dead weight), or as the distribution of responses generated by these consequences (the functional operant response class, e.g., lever presses varying between 5g and 20g) (Catania, 1973). The concentration of responses within the reinforced class is called differentiation, whereas the spread of responses outside the reinforced class is called induction (Catania, 1984). Few studies have focused on the effects of psychomotor stimulating drugs on spatial and temporal aspects of operant behavior (see Iversen & Mogensen, 1988; Sagvolden, Slatta, & Arntzen, 1988). Actually, most behavioral studies do not record responses outside the reinforced class. This is an important methodological problem, because stimulant drugs are believed to increase the proportion of responses outside the reinforced class (Lyon & Randrup, 1972; Morrison & Stephenson, 1973; Weissman, 1966). Is it possible that the reduced response rates sometimes observed following stimulant-drug administration result from changes in the topography of the operant response, that is, induction and change of the functional operant, and not from any general reduction in the rate of the functional operant?

The present study was designed to determine whether commonly observed high dose stimulant-induced reductions in operant responding can be explained by (a) a simple reduction in the frequency of the operant response or (b) the occurrence of predictable alterations in the spatial and temporal characteristics of the operant response. Spatial induction, spatial and temporal response variability, and response chains were studied by using a holeboard with 20 different response locations available to the animal.

Methods

Subjects

Six Moll-Wistar rats served as subjects in the experiment. The animals were obtained from Mollegaard Breeding Center, Denmark. At the start of the experiment, the animals were 60 days old and weighed 160-180 g. They were kept individually in cages, 42.0 x 26.5 x 14.5 cm, in a room where the temperature was 20[degrees]C and with lights on from 1100 to 2300 hours. Food was available ad lib. when the animals were in their home cages. Water was available 1 h per day immediately after each session.

Apparatus

The apparatus is described by Sagvolden et al. (1 988). In brief, a 1-[m.sup.3] LVE electrophysiological cubicle, with a one-way screen in the front door, was used as the observation chamber. A standard BRS/LVE Rodent Test Cage (RTC-022) was placed inside. The Plexiglas door was replaced by a metal holeboard, 25.9 x 30.3 x 0.5 cm, with 20 holes, each with a diameter of 2.0 cm. On the outside, the holes were named alphabetically from A to T, top to bottom and left to right (cf. Figure 1). The holes were arranged in five parallel columns, each with four holes. The horizontal center-to-center distance between holes was 3.5 cm, and the vertical center-to-center distance was 6.1 cm. The bottom row was 4.0 cm above the floor level and the top row was 9.4 cm below the ceiling of the cage. Nose-pokes in Hole J were reinforced by 0.01 ml tap water from a Liquid Dipper (Model SLD-002) 11.8 cm from the response panel and 3 cm above the floor in the standard location of the RTC-022 test cage. Holes S and T were therefore closer to the dipper than any other hole. The cage had no levers or Lights except the 15-W house light, which illuminated the cage during sessions. "White" masking noise, approximately 75dB, was produced by a tape recorder.

Procedure

The experiment was run daily 7 days a week between 1600 and 2300 hours. The animals were deprived of water for 22.5 h. Following each session, the rat was returned to its home cage and given free water for 1 h. Pokes in Hole J were reinforced according to a fixed-interval 60-s schedule Fl 60). The 60-s interval was divided into six consecutive 10-s segments, with a seventh segment running from when the reinforcer was programmed to the occurrence of a reinforced response. The procedure is described in detail by Sagvolden et al. (1988). The present data were collected during the same sessions as the ones reported in the previous article, but focusing on other aspects of behavior.

In order to habituate the animals to injections, there were 1 0 sessions alternating between no injection and an injection of physiological saline at a volume of 1 ml/kg body weight. All injections of room-temperature saline and methylphenidate hydrochloride (Ritalin[R]), provided by Ciba-Geigy Norway, were given i.p. 25 min before each session. The drug was dissolved in physiological saline in concentrations of 1.0, 3.0, 6.0, 9.0,12.0, and 15.0 mg/ml. The doses were administered in the following sequence: 3, 6, 1, 9, 3, 6, 1, 9, 15, 12, 12, and 15 mg/kg. Between sessions with injections of methylphenidate, three sessions were run in the following order: no injection, injection of saline, and no injection.

The onset of each session was signaled by turning the house light on, and the termination by turning the light off. Each session started with a 5-6 min "warm-up" period. The recording session started immediately after the last reinforcement in the warm-up period; or if no nose-poke in J had occurred, after 6 min. The recording session consisted of 20 fixed intervals but lasted not more than 21 min, whichever occurred first.

Behavior Recorded

The exact order and time of occurrence of nose-pokes in the different response locations were recorded throughout the entire session.

Index of Variability

An index of variability was calculated as the ratio between the total number of different three-poke sequences divided by the sum of three-poke sequences, for example, JKJ, KJK, JKJ, KJK constitutes two different sequences KJK and JKJ, but the total number of sequences is four.

Index of Curvature

Increases or decreases of local response rates during fixed intervals may be described mathematically by an index of curvature (I.C.; Fry, Kelleher, & Cook, 1960). A high positive index shows that there is a pronounced acceleration of the response rate throughout the Fl, and a high negative index shows that there is a pronounced deceleration.

Results

Baseline responses, as well as responses following saline injections, were never restricted to the |correct' hole, the descriptive operant class of responses, but involved a few neighboring holes, especially at the end of each 60-s fixed interval (Figure 1). However, responses spread to even more holes as the dose increased up to 9 mg/kg. This development was reversed following even higher doses, when the nose-pokes became increasingly stereotyped and were gradually restricted to fewer response locations, especially those in one of the lower comers of the holeboard.

The spatial distribution of responses was different in the first part, as compared to the last part, of the fixed interval in undrugged rats (Figure 2). Forty-eight percent of the responses in the first 30 s were located in T, and 2% were located in T in the last 20 s of the interval. Responses in J represent 12% of the total for the first 30 s, and 47% for the last 20 s of the interval. Thus, responses were relatively spread out on the holeboard during the initial 30 s of the interval. In the last 20 s of the interval, however, the majority of responses were located in J and neighboring holes.

In the last 20 s of the interval, 65% of all two-poke combinations were either JJ, JK, or KJ. As Figure 3 shows, this percentage decreased by increasing dose. Following the 1-mg/kg and 3-mg/kg doses, the JJ sequence was most affected. The frequency of these three predominant sequences was markedly decreased after administration of the 6-mg/kg and 9-mg/kg doses, with a total absence of the sequence JJ after the 9-mg/kg dose. J-responses were almost nonexistent following the highest doses.

Figure 4 shows how the variability of three-poke sequences changed as a function of dose and time in the interval. A high value of the index means high variability, that is, that few three-poke sequences were repeated. The different values are calculated as the mean of two sessions for six rats for the 0-, 1-, 3-, 6- and 9-mg/kg dose, and as the mean of two sessions for two rats for the 12- and 15-mg/kg dose. Following saline administration, sequence variability was high in the initial segments of the Fl and low in the final segment. The index of variability decreased by increasing dose in the first 40 s, but increased by dose in the final 20 s of the interval. After the highest doses, there were no differences between the early and the late part of the interval.

The index of curvature (I.C.) for J pokes showed higher values for all doses than the I.C. for total pokes (Figure 5). The I.C. for J pokes was not calculated for the 15-mg/kg dose because of low response rates. For the same reason, the I.C. for total responses is the mean of only four rats following the 15-mg/kg dose.

Compared to the results following saline administration, the reinforcement density did not change following 1-, 3-, and 6-mg/kg injections, but a slight decrease was observed following the 9-mg/kg dose and a large decrease was seen when the dose was more than 9-mg/kg.

Discussion

The main purpose of the present study was to investigate how methylphenidate affects the functional and descriptive operant, that is, spatial and temporal distributions of responses generated by an Fl 60-s schedule of reinforcement. The results will be analyzed in terms of effects on response stimulation (temporal and spatial induction), response variability, and response chains.

Differential effects of psychomotor stimulants on operant behavior may be caused by competition and interaction between different behaviors. Such a hypothesis has been proposed by Lyon and Robbins (1975). They suggested that amphetamine has a response-stimulatory effect, that is, the repetition rate of all motor activities increases following drug administration. Activities will compete for access to the behavioral repertoire of the animal. High response rates are likely to be reduced because the operant behavior occupies almost all the time available. Low operant response rates are likely to increase, because the amount of time spent on each response is reduced, and because behaviors that require long pauses are the first to disappear f rom the behavioral repertoire.

The present results show that the high dose stimulant-induced reductions in the 'correct' response were caused by systematic alterations in the spatial and temporal characteristics of the functional operant response class and not a simple reduction of operant responding.

Administration of methylphenidate resulted in an increasing number of responses involving holes other than J (the "correct" hole) and in many instances the repetitive two-hole sequences in the middle column (involving J) moved to columns to the left following methylphenidate. Rats frequently repeating the K-J sequence started to repeat the sequences G-F or C-B following moderate and high doses of the drug. This effect decreased the rate of J-response without changing the total number of responses. Following low and medium doses, variability of response locations increased late in the interval as the repetitive response sequences that were dominating during baseline gradually disappeared. These results show that the functional operant is shifted on the response panel.

Undrugged, all rats showed repetitive sequences of responding in the last 20 s of the Fl. The most frequent two-response sequences were JJ and KJ; the most frequent three-response sequence was LKJ. The repetitive response sequences disappeared gradually with increasing doses of methylphenidate. This result is in accordance with several studies of the effects of stimulant drugs on response chains (Thompson, 1975; Thompson & Moerschbaecher, 1979). The longest repetitive response sequences involving three holes disappeared first and were replaced by shorter sequences. This may indicate that response-stimulatory effects of methylphenidate caused new response sequences to start before the preceding sequence was completed. The gradual shortening of responses observed in the present experiment supports the Lyon-Robbins (1975) hypothesis.

The present study has shown that traditional operant recording devices may not be suitable for recording all the responses induced by psychomotor stimulants because responses may be emitted apart from the lever or key, or be of insufficient force to activate the recording device. In accordance with the Lyon-Robbins hypothesis (1975), the present results indicate that incomplete responses may cause the apparent reduction of high-rate responding following drug administration when traditional recording devices are used. Thus it may be important to use procedures that differentiate between the descriptive and the functional operant when studying the effects of psychomotor stimulants. It could be that the frequently reported rate-decreasing effects of high doses of stimulants (for reviews, see, e.g., Lyon & Robbins, 1975; Robbins et al., 1989; Sanger & Blackman, 1976) reflect the tact that most studies have focused on the descriptive operant rather than the functional operant.

References

BRANCH, M. N. (1984). Rate dependency, behavioral mechanisms, and behavioral pharmacology. Journal of the Experimental Analysis of Behavior, 42, 511-522 CATANIA, A. C. (1973). The concept of the operant in the analysis of behavior Behaviorism, 1, 103-116 CATANIA, A. C. (1 984). Learning (2nd ed.). Englewood Cliffs, NJ: Prentice-Hall. DEWS, P. B. (1955). Studies on behavior. 11. The effects of pentobarbital, methamphetamine and scopolamine on performances in pigeons involving discriminations. Journal of Pharmacology and Experimental Therapeutics, 115, 137-147. DEWS, P. B. (1958). Studies on behavior. IV. Stimulant actions of methamphetamine. Journal of Pharmacology and Experimental Therapeutics, 122, 137-147. DEWS, P. B., & WENGER, G. R. (1977). Rate-dependency of the behavioral effects of amphetamine. In C. T. Thompson & P. B. Dews (Eds.), Advances in behavioral pharmacology (Vol. 1, pp. 167-227). New York: Academic Press. FRANZ, D. N. (1985). Central nervous system stimulants: Strychnine, picrotoxin, pentylenetetrazol, and miscellaneous agents (Doxapran, Nikethamide, Methylphenidate). in A. G. Gilman, L. S. Goodman, T W. Rall, & F. Murad (Eds.), The pharmacological basis of therapeutics (pp. 582-588). New York: MacMillan. FRY, W., KELLEHER, R. T., & COOK, L. (1960). A mathematical index of performance on fixed-interval schedules of reinforcement. Journal of the Experimental Analysis of Behavior, 3,193-199. GITTELMAN KLEIN, R., & ABIKOFF, H. (1989). The role of psychostimulants and psychosocial treatments in hyperkinesis. In T. Sagvolden & T. Archer (Eds.), Attention deficit disorder Clinical and basic research (pp. 167-180). Hillsdale, NJ: Erlbaum. IVERSEN, I. H., & MOGENSEN, J. (1988). A multipurpose vertical holeboard with automated recording of spatial and temporal response patterns for rodents. Journal of Neuroscience Methods, 25, 251-263. LYON, M., & RANDRUP, A. (1972). The dose-response effect of amphetamine upon avoidance behavior in the rat seen as a function of increasing stereotypy. Psychopharmacologia, 23, 334-347. LYON, M., & ROBBINS, T. W. (1975). The action of central nervous system stimulant drugs: A general theory concerning amphetamine effects. In W. Essman & L. Valzelli (Eds.), Current developments in psychopharmacology (pp. 79-163). New York: Spectrum. MORRISON, C. F., & STEPHENSON, J. A. (1973). Effects of stimulants on observed behavior in rats on six operant schedules. Neuroscience, 12, 297-310. ROBBINS, T. W., JONES, G. H., & SAHAKIAN, B. J. (1989). Central stimulants transmitters and attentional disorder: A perspective from animal studies. In T. Sagvoiden & T. Archer (Eds.), Attention deficit disorder: Clinical and (pp. 199-222). Hilisdale, NJ: Erlbaum. basic research (pp .199 SAGVOLDEN, T., JENSSEN, J. R., & BRORSON, 1. W. (1983). Rate-dependent effects of methylphenidate (Ritalin) on fixed-interval behavior in rats. Scandinavian Journal of Psychology, 24, 231-236. SAGVOLDEN, T., SLATTA, K., & ARNTZEN, E. (1988). Low doses of methylphenidate (Ritalin) may alter the delay-of-reinforcement gradient. Psychopharmacology, 95,303-312. SANGER, D. J., & BLACKMAN, D. E. (1 976). Rate-dependent effects of drug: A review of the literature. Pharmacology, Biochemistry & Behavior, 4, 73-83. SOLANTO, M. V. (1986). Behavioral effects of low dose methylphenidate in childhood attention deficit disorder: Implications for a mechanism of stimulant drug action. Journal of American Academy of Child Psychiatry, 25, 96-101. THOMPSON, D. M. (1975). Repeated acquisition of response sequences: Stimulus control and drugs. Journal of the Experimental Analysis of Behavior, 23, 429-436. THOMPSON, D. M., & MOERSCHBAECHER, J. M. (1979). An experimental analysis of the effects of d-amphetamine and cocaine on the acquisition and performance of response chains in monkeys. Journal of the Experimental Analysis of Behavior, 32, 433-444. WEISSMAN, A. (1966). Apomorphine elicitation of key pecking in a pigeon. Archives of International Pharmacodynamics, 160, 330-332.

Erik Arntzen is now at Bleiker Treatment House, Bleikerfaret 4, N-1370 Asker, Norway. Knut Slatta is now at Ragna Ringdale Dagsenter, H. N. Hauges gt. 44, N-0481 OSLO, Norway.

The study was supported by Grant 326.91/039 from the Research Council of Norway, and by the University of Osio.

Reprint requests may be sent to Terje Sagvoiden, Institute of Neurophysiology, University of Osio, P. O. Box 11 04 BLINDERN, N-0317 OSLO, Norway.
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Author:Arntzen, Erik; Sagvolden, Terje; Slatta, Knut
Publication:The Psychological Record
Date:Mar 22, 1993
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