Effects of amphetamine-CNS depressant combinations and of other CNS stimulants in four-choice drug discriminations

Abstract

Three pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg amphetamine, a combination of these two drugs at these doses, and saline using a four-choice procedure (amphetamine-pentobarbital group). Three other pigeons were trained to discriminate among 5 mg/kg morphine, 2 mg/kg methamphetamine, a combination of these two drugs at these doses, and saline (methamphetamine-morphine group). After 10 to 13 months of training, the pigeons averaged more than 90% of their responses on the appropriate key during training sessions. In subsequent testing, dose-response curves were determined for the individual drugs, for a wide range of dose combinations of the training drugs, and for two drugs to which the pigeons had not been exposed previously (pseudoephedrine and nicotine). After low test doses of the training drugs, pigeons responded on the saline key. As the dose increased, responding on the key associated with that drug during training sessions increased. When training drugs were combined at doses that were not discriminable when given alone, responding occurred on the saline key. When a discriminable dose of one training drug was combined with a nondiscriminable dose of the other training drug, responding occurred on the key associated with the discriminable dose. When both drugs were given at discriminable doses, responding almost always occurred on the drug-combination key. The response-rate decreasing effects of pentobarbital and amphetamine were mutually antagonized when the drugs were combined, but the rate-decreasing effects of morphine and methamphetamine were not. After low doses of pseudoephedrine and nicotine, pigeons in both groups responded on the saline key. After higher doses of pseudoephedrine and nicotine, responding in the amphetamine-pentobarbital group occurred primarily on the amphetamine key. In the methamphetamine-morphine group, higher doses of pseudoephedrine and especially nicotine engendered more responding on the combination key than had occurred in the other group. The four-choice procedure can reveal subtle effects in the discrimination of individual drugs and drug combinations that are not apparent with procedures offering fewer response alternatives.

Fig. 1. Patterns of responding on each key following increasing doses of pentobarbital and amphetamine in pigeons trained to discriminate among saline, pentobarbital, amphetamine, and a combination of pentobarbital and amphetamine (amphetamine–pentobarbital group).

The top row shows the pentobarbital dose-response curve determined using single-dose procedures and the second row shows the pentobarbital dose-response curve determined using cumulative-dose procedures. The bottom two rows show amphetamine dose-response curves determined using single-dose procedures (third row) and using cumulative-dose procedures (fourth row). The columns show data for individual pigeons. Abscissae: Doses of pentobarbital or amphetamine in mg/kg. Ordinate: Percentage of responses on each key. Response-key designations are shown in the lower left corner of the figure.

Fig. 2. Patterns of responding on each key following increasing doses of morphine and methamphetamine in pigeons trained to discriminate among saline, morphine, methamphetamine, and a combination of morphine and methamphetamine (methamphetamine–morphine group).

The top two rows show morphine dose-response curves determined using single-dose procedures (first row) and using cumulative-dose procedures (second row). The bottom two rows show methamphetamine dose-response curves determined using single-dose procedures (third row) and using cumulative-dose procedures (fourth row). The columns show data for individual pigeons. Abscissae: Doses of morphine or methamphetamine in mg/kg. Ordinate: Percentage of responses on each key. Response-key designations are shown in the lower left corner of the figure.

Fig. 3. Pattern of responding on each key following increasing doses of amphetamine in the presence of increasing doses of pentobarbital in pigeons in the amphetamine–pentobarbital group.

The columns show data from individual pigeons. Each row shows the dose-response effects of amphetamine in combination with a different dose of pentobarbital. Abscissae: Doses of amphetamine in mg/kg. Ordinate: Percentage of responses on each key. Response-key designations are shown in the lower left corner of the figure.

Fig. 4. Pattern of responding on each key following increasing doses of methamphetamine in the presence of increasing doses of morphine in pigeons in the methamphetamine–morphine group.

The columns show data from individual pigeons. Each row shows the dose-response effects of methamphetamine in combination with a different dose of morphine. Abscissae: Doses of methamphetamine in mg/kg. Ordinate: Percentage of responses on each key. Response-key designations are shown in the lower left corner of the figure.

Fig. 5. A comparison of single-dose test procedures with cumulative-dose test procedures for the study of drug combinations.

The top two rows compare amphetamine and pentobarbital combinations under the two dosing procedures tested in the amphetamine–pentobarbital group. The bottom two rows compare methamphetamine and morphine combinations under the two procedures in the methamphetamine–morphine group. For both drug combinations, the first row shows results from single-dose procedures, and the second row shows results from cumulative-dose procedures. The columns show data for the individual pigeons. Abscissae: Dose of amphetamine (top two rows), or methamphetamine (bottom two rows), in mg/kg. Ordinate: Percentage of responses on each key. Response-key designations are shown in the lower left corner of the figure.

Fig. 6. Effects of pseudoephedrine and nicotine determined using cumulative-dose procedures in pigeons in the amphetamine–pentobarbital group.

The top two rows show pseudoephedrine dose-response curves determined on two separate occasions, and the bottom two rows show nicotine dose-response curves determined on two separate occasions. The columns show data for individual pigeons. NR indicates that the pigeon did not respond on any key following this dose. Abscissae: Doses of pseudoephedrine (top two rows) or nicotine (bottom two rows) in mg/kg. Ordinate: Percentage of responses on each key. Response-key designations are shown in the lower left corner of the figure.

Fig. 7. Effects of pseudoephedrine and nicotine determined using cumulative-dosing test procedures in pigeons in the methamphetamine–morphine group.

The top two rows show pseudoephedrine dose-response curves determined on two separate occasions, and the bottom two rows show nicotine dose-response curves determined on two separate occasions. The columns show data for individual pigeons. Abscissae: Doses of pseudoephedrine (top two rows) or nicotine (bottom two rows) in mg/kg. Ordinate: Percentage of responses on each key. Response-key designations are shown in the lower left corner of the figure.