Tolerance to Cocaine's Rate‐increasing Effects Upon Repeated Administration

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Key pecking by 4 pigeons was maintained by a multiple schedule consisting of two variable-interval 60-s schedules wherein each food presentation followed a nonresetting 27-s delay that was either briefly signaled at its outset or completely signaled. Brief-signal duration was adjusted so that response rates maintained by the briefly and completely signaled delays of reinforcement were similar. In general, acute administration of small to intermediate doses (0.3 to 3.0 mg/kg) of cocaine produced either small increases in response rates in both components or no change, and larger doses (5.6 to 13.0 mg/kg) decreased response rates. Chronic (i.e., daily) cocaine administration (10.0 mg/ kg) resulted in tolerance to the rate-decreasing effects in both components. Cocaine's effects were generally similar whether delays were completely or briefly signaled. Discontinuation of cocaine administration and subsequent removal of the delay signals also had similar effects in both components of the multiple schedule. Taken together, these results are consistent with the view that the two types of delay signals were equally effective in maintaining responding during the variableinterval schedules.Key words: signaled delay of reinforcement, conditioned reinforcement, cocaine, tolerance, variableinterval schedule, key peck, pigeonsThe purpose of the present experiment was to study the effects of acute and chronic (i.e., daily) cocaine administration on responding maintained by briefly and completely signaled delays to reinforcement. Key pecking by 4 pigeons was maintained by a multiple schedule consisting of two variableinterval (VI) 60-s components, wherein each reinforcer followed a 27-s delay. In one component the delay was briefly signaled by a change in key color at its beginning; in the other component the delay was completely signaled. Roughly equal response rates were established in the two components of the multiple schedule via manipulation of the brief-signal duration. Cocaine was administered acutely and then chronically to determine whether drug effects on performance would differ for the two types of signaling arrangements.Cocaine was chosen for study in the present experiment because it has been suggested that this drug and other psychomotor stimu-

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confidence: 99%

Effects of Cocaine on Briefly Signaled Versus Completely Signaled Delays to Reinforcement

Walker

Branch

1996

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“…It is possible, however, that subjects also become more sensitive to the rate-increasing effects of low doses of drug when they are deprived of food. One of the more reliable generalizations from behavioral pharmacological research is that behavior that occurs at low rates is often increased by drugs, a fact that gave rise to the rate-dependency principle (Dews, 1958 (Barrett, 1976;Byrd, 1979;Dews, 1958Dews, , 1964Howell, Byrd, & Marr, 1986;Kelly & Thompson, 1988;Schama & Branch, 1994;Spealman, Goldberg, Kelleher, Goldberg, & Charlton, 1977;Spealman, Madras, & Bergman, 1989;Wenger, Donald, & Cunny, 1986;Zuccarelli & Barrett, 1980;see Kelleher & Morse, 1968, for a review). Rateincreasing effects of drugs are conveniently studied using fixed-interval (FI) schedules.…”

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confidence: 99%

Cocaine's Effects on Food‐reinforced Pecking in Pigeons Depend on Food‐deprivation Level

Schaal

Miller

Odum

1995

Four pigeons deprived to 80% of their laboratory free-feeding weights pecked keys under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food presentation. Components alternated strictly with 15-s timeouts separating them; each was presented six times. When rates of pecking were stable, 2 pigeons' weights were reduced to 70%, and the other 2 pigeons' weights were increased to 82.5% to 85% of free-feeding levels. Cocaine (1.0, 3.0, 5.6, and 10.0 mg/kg and saline) was administered 5 min prior to sessions. When each dose had been tested twice, pigeons' weights were adjusted to the level that they had not yet experienced, and cocaine was tested again. Cocaine reduced response rates in a dose-dependent manner under the fixed-ratio schedule and under the fixed-interval schedule at high doses, and increased rates under the fixed-interval schedule at low doses. Reductions in pecking rates occurred at lower doses under both schedules in 3 of 4 pigeons when they were less food deprived compared to when they were more food deprived. Low doses of cocaine increased low baseline rates of pecking in the initial portions of the fixed-interval schedules by a greater magnitude when pigeons were more food deprived. Thus, food-deprivation levels altered both the rate-decreasing and rate-increasing effects of cocaine. The implications of these results for the mechanisms by which food deprivation increases cocaine self-administration and for the dependence of cocaine's effects on the baseline strength of operant behavior are discussed.Key words: cocaine, fixed-interval schedules, fixed-ratio schedules, food deprivation, key peck, pigeon Changes in levels of food deprivation of nonhuman subjects have been shown to alter several behavioral effects of drugs profoundly. Studies have shown that the rate-suppressive effects of drugs on operant behavior are obtained at lower doses when animals are less food deprived than when they are more severely food deprived (Cole, 1967;Gollub & Mann, 1969;Kelly & Thompson, 1988;Samson, 1986;Schaal & Branch, 1992

“…In an operant-conditioning paradigm, environmental factors, like the schedule of reinforcement, can cause an interaction between the drug and behavior, largely determining the effects that a drug exerts on behavior, rather than its effects depending solely on known pharmacological properties (Barrett, 1976;Dews, 1955Dews, , 1958Gonzales & Goldberg, 1977;Kelleher & Morse, 1964, 1968. For example, cocaine can produce dose-dependent rate-decreasing effects on responding maintained by fixed-ratio (FR) food reinforcement (e.g., Hoffman, Branch, & Sizemore, 1987) and dose-dependent rate-increasing effects on responding maintained by fixed-interval (FI) food reinforcement (e.g., Schama & Branch, 1994).…”

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confidence: 99%

Tolerance to cocaine's effects following chronic administration of a dose without detected effects on response rate or pause

Minervini

Branch

2013

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To observe tolerance to drug effects on operant behavior, the dose that researchers have often selected for chronic administration is one that disrupts, but does not abolish, responding. Some evidence suggests that tolerance may develop after chronic administration of relatively smaller doses. The purpose of the present experiment was to assess systematically effects of chronic administration of a dose without detected effect on responding. Specifically, response rates and postreinforcement pauses of five pigeons key pecking under a three-component multiple fixed-ratio schedule of food reinforcement were observed under chronic cocaine administration. We evaluated the effects of a range of doses (1.0 mg/kg to 17.0 mg/kg) during acute administration. The largest dose that failed to alter responding acutely then was administered chronically (1.0 mg/kg for one pigeon, 3.0 mg/kg for three pigeons, and 5.6 mg/kg for one pigeon). After 30 consecutive sessions of chronic administration, smaller and larger doses occasionally were substituted for the chronic dose. Pigeons then received presession saline administration for 30 consecutive sessions, and the postchronic effects of the series of doses on responding were determined. All subjects developed tolerance to doses of cocaine that initially had caused large decreases in rate, with the magnitude of the effects varying across components of the multiple schedule and subjects. Specifically, tolerance generally was greatest in the components with smaller ratios. Following postchronic saline administration, tolerance was usually diminished. Overall, the results demonstrate that under these conditions, repeated experience with disruptive effects of cocaine on food-maintained responding is not a necessary factor in the development of tolerance.