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At least 271 records · Page 15Linked to original sources
PubMed1989

Effects of cocaine and related drugs in nonhuman primates. II. Stimulant effects on schedule-controlled behavior.

The behavioral effects of cocaine were compared with those of several cocaine derivatives and structurally distinct drugs that inhibit monoamine uptake. Squirrel monkeys were trained to respond under a fixed-interval schedule of stimulus-shock termination, and dose-effect curves were determined by administering cumulative doses i.v. Among the cocaine congeners, (-)-cocaine, (+)-pseudococaine and 1 alpha H, 3 alpha, 5 alpha H-tropan-3-yl-3,5-dichlorobenzoate produced dose-related increases in response rate, whereas (-)-pseudococaine, (-)-benzoylecgonine and (-)-benzoylnorecgonine did not increase responding consistently over a 100-fold or greater range of doses. 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine, which selectively inhibits uptake of dopamine, and mazindol, methylphenidate, nomifensine and bupropion, which inhibit uptake of dopamine as well as other monoamines, had behavioral effects similar to those of cocaine. In contrast, desipramine and citalopram, which selectively inhibit uptake of norepinephrine and serotonin, respectively, produced only dose-related decreases in response rate. The results combined with previous studies demonstrate a close correspondence between the potencies of 15 different drugs for producing cocaine-like behavioral effects and for displacing specifically bound [3H]cocaine in caudate-putamen. These findings are consistent with the view that the behavioral effects of cocaine and related drugs are linked to their actions at specific cocaine recognition sites associated with the dopamine uptake system.

Animals↗
PubMed1985

Effects of serotonin receptor agonists and antagonists on schedule-controlled behavior of squirrel monkeys.

The behavioral effects of the serotonin (5-HT) precursor l-5-hydroxytryptophan (l-5-HTP) and the phenylpiperazine 5-HT agonists 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), 1-(m-trifluromethylphenyl) piperazine (TFMPP), 1-(m-chlorophenyl)piperazine (CPP) and 2-(1-piperazinyl)quinoline (quipazine) were compared with those of the putative 5-HT antagonists metergoline, methysergide, cyproheptadine, cinanserin and ketanserin under a multiple 5-min fixed-interval schedule of food or electric shock presentation in squirrel monkeys. Intramuscular administration of l-5-HTP (0.3-17 mg/kg), MK-212 (0.01-1.0 mg/kg), TFMPP and CPP (0.03-10 mg/kg) produced dose-related decreases in responding under both the food- and shock-presentation schedules. Quipazine differed from the other 5-HT agonists in that it increased shock-maintained behavior at doses (0.1-1.0 mg/kg) that decreased responding maintained by food. The 5-HT antagonists produced mixed behavioral effects. Metergoline (0.03-1.0 mg/kg), cyproheptadine (0.1-1.0 mg/kg) and cinanserin (1.0-10 mg/kg) produced dose-related increases in responding maintained by food, whereas only metergoline and methysergide increased behavior maintained by shock presentation. The prototype 5-HT2-receptor ligand ketanserin (0.3-10 mg/kg) differed from the other 5-HT antagonists in that it decreased behavior maintained by either event. Thus, performances maintained by food or shock presentation reveal both qualitative and quantitative differences in the behavioral effects of 5-HT receptor agonists and antagonists.

5-Hydroxytryptophan↗
PubMed1988

Schedule-controlled behavior in infant and juvenile monkeys exposed to lead from birth.

Monkeys (Macaca fascicularis) were dosed orally from birth with 0 or 2000 micrograms/kg/day of lead as lead acetate. Blood lead concentrations of treated monkeys peaked at an average of 115 micrograms/dl by 100 days of age, and decreased to a steady state level of 33 micrograms/dl after withdrawal from infant formula at 270 days of age. No overt signs of toxicity were observed. Beginning at 60 days of age, monkeys were tested on a fixed ratio (FR) schedule of reinforcement, followed by a fixed interval (FI) schedule. Infants were tested in their home cages for 16 hours each day. When these monkeys reached three years of age, performance on a multiple fixed interval-fixed ratio schedule was evaluated. Infant performance was characterized by increased FR pause and decreased FI pause in the treated monkeys. Juvenile performance of lead-treated monkeys was characterized by increased Fl run rate, pause time, and index of curvature. Treated monkeys exhibited increased variability of performance both within and between sessions on several measures of Fl and FR performance.

Animals↗
PubMed1986

Effects of ethylketazocine and morphine on schedule-controlled behavior in pigeons and squirrel monkeys.

The behavioral effects of morphine and ethylketazocine were compared in squirrel monkeys and pigeons responding under fixed-interval schedules of food presentation, and in monkeys responding under fixed-interval schedules of electric-shock presentation. Both morphine and ethylketazocine produced dose-related decreases in rates of responding maintained by food presentation in either species. However, intermediate doses of both drugs increased rates of responding maintained by shock presentation in monkeys; at higher doses both drugs decreased rates of shock-maintained responding. In monkeys and pigeons, the dose-effect curves for both ethylketazocine and morphine were shifted to a comparable degree of naloxone. Maximal effects of morphine were observed 16 to 24 min after injection and typically lasted the entire 40-min observation period. Effects of ethylketazocine had a faster onset (maximal effects were observed by 8 to 16 min after injection), and shorter duration (effects diminished by 24 to 40 min after injection). Ethylketazocine was 30 to 100 times more potent than morphine under either the schedule of food or shock presentation in squirrel monkeys, whereas the two drugs had similar potencies in pigeons. Thus, the effects of at least one of the drugs may be mediated differently in one of the two species.

Animals↗
PubMed1985

Effects of drugs on schedule-controlled behavior in rats during chronic haloperidol administration.

Dose-response curves for haloperidol, phencyclidine, morphine, meperidine and cimetidine were determined in rats trained under a multiple fixed-ratio 30, fixed-interval 5-min schedule of reinforcement. Haloperidol, morphine, meperidine and cimetidine decreased both fixed-ratio and fixed-interval rates of responding. Phencyclidine had a biphasic effect on overall response rates in both components: response rates increased and then decreased as the dose was increased. After these dose-response curve determinations, chronic daily treatment with haloperidol (0.3 mg/kg i.p.), after the behavioral session, was initiated. After 6 weeks of chronic treatment with haloperidol, the dose-response curves were redetermined for all the drugs, while haloperidol continued to be administered after the session. During chronic haloperidol administration, the dose-effect curves for haloperidol, morphine, meperidine and cimetidine were not modified consistently; however, chronic haloperidol treatment enhanced the effects of phencyclidine as shown by a shift of the dose-response curves to the left during both fixed-ratio and fixed-interval components. Four weeks after chronic haloperidol had been discontinued, low doses of haloperidol produced smaller rate-decreasing effects than they had previously.

Animals↗
PubMed1977

Some effects of cocaine and two cocaine analogs on schedule-controlled behavior of squirrel monkeys.

The behavioral effects of two phenyltropane derivatives of coaine were compared with those of cocaine. Squirrel monkeys responded under multiple fixed-interval, fixed-ratio schedules of either stimulus-shock termination or food presentation or under a fixed-ratio schedule of food presentation. The effects of the three drugs were independent of the type of event that maintained responding. Under the fixed-interval schedules, some doses of each drug increased responding, whereas larger doses generally decreased responding. Maximal increases in responding were similar with each drug. Appropriate doses of each drug increased low response rates, which occurred during the initial segments of the fixed intervals, but had little effect on or decreased higher response rates, which occurred during the later segments of the fixed intervals. Under the fixed-ratio schedules, each drug decreased responding in a dose-related manner. Decreases in fixed-ratio responding resulted both from increased periods of no responding at the beginning of the fixed ratios and from decreased rates of responding once responding began. Each cocaine analog had a slower onset of effect and longer responding began. Each cocaine analog had a slower onset of effect and a longer duration of effect than cocaine. The behavioral effects of the two cocaine analogs were qualitatively similar to those of cocaine, but each was 3 to 10 times more potent than cocaine.

Animals↗