Stimulus Properties Of D-amphetamine Research Articles

FACILITATORY AND INHIBITORY ACTIONS OF MORPHINE ON THE DISCRIMINATIVE STIMULUS PROPERTIES OFD-AMPHETAMINE

Facilitatory and inhibitory actions of morphine on the discriminative stimulus properties ofD-amphetamine were examined in rats trained to discriminateD-amphetamine (1 mg kg−1) from saline in a two–lever food reinforced operant task. Morphine (0.625–2.5 mg kg−1) did not itself generalize to amphetamine. When the percentages of rats selecting the drug–appropriate lever were plotted as a function of the individual lowest generalized dose (LGD), a log–linear model fitted to cell frequency indicated a ‘morphine×amphetamine×lever selection’ interaction. Subsequent comparisons indicated that morphine significantly increased or decreased drug lever selection in rats receiving one–half LGD or LGD, respectively. In both cases no difference was found among morphine doses. The present study confirms that the discriminative stimulus properties of amphetamine can be both potentiated and attenuated by morphine. The direction to which morphine modulates the interoceptive effects of 1 mg kg−1amphetamine seems to be dependent on the individual sensitivity of animals to amphetamine rather than on the overall effect of the test dose of amphetamine alone.

Influence of some drugs of abuse on the discriminative stimulus properties of amphetamine

The present study assessed the utility of a drug interaction paradigm for measuring the effects of various psychoactive drugs on the stimulus properties of d-amphetamine. In the first experiment, rats trained to discriminate 1.0mg/kg d-amphetamine from saline were tested for generalization to a range of d-amphetamine doses (0.25, 0.50 and 1.0mg/kg) injected alone or with cocaine, apomorphine or haloperidol. When given alone d-amphetamine yielded an orderly dose-response function and this was altered by the test drugs in a manner consistent with the dopamine agonist or antagonist actions of each compound. In the second experiment, the cueing effects of d-amphetamine were potentiated by nicotine and attenuated by morphine and midazolam. Ethanol enhanced the cueing effects of the lower d-amphetamine doses but produced no drug-lever responding when given alone. These findings confirm the results of previous studies which have assessed the effects of these classes of drugs on the stimulus properties of amphetamine. However, the results are inconsistent with the hypothesis that all drugs of abuse possess psychomotor stimulant properties.

Amphetamine-like stimulus properties produced by electrical stimulation of reward sites in the ventral tegmental area

The present study examined whether the stimulus properties of d-amphetamine could be mimicked by electrical stimulation of the ventral tegmental area (VTA). Rats trained to discriminate 1.0 mg/kg d-amphetamine from saline were given generalization tests with a range of d-amphetamine doses administered either alone or in combination with VTA stimulation. The results suggested that the VTA stimulation could enhance the cueing effects of d-amphetamine, as levels of responding on the d-amphetamine-appropriate lever during stimulation trials were increased relative to tests without stimulation. Individual differences were observed in the amount of drug-lever responding elicited by the VTA stimulation during drug-free substitution tests, and the different levels of drug-lever responding correlated positively with the response rates obtained from these rats during subsequent intracranial self-stimulation tests. These findings suggest that VTA stimulation can have d-amphetamine-like stimulus properties and such stimulus properties may be related to the rewarding effects of the brain stimulation.

Effects of nimodipine on the discriminative stimulus properties of d-amphetamine in rats.

The discriminative stimulus (DS) properties of d-amphetamine (AMP) are thought to be mediated by enhanced release of catecholamines, which may involve neuronal calcium influx through voltage sensitive channels. The present study examined the influence of nimodipine, a calcium channel blocker, on the DS properties of AMP. Rats (N = 8) were trained to discriminate AMP (0.5 mg/kg, IP) from saline in a two-lever, food-reinforced, drug discrimination paradigm. Nimodipine alone (2.0-5.6 mg/kg, IP) did not substitute for AMP. When given in combination with AMP, 2.0 mg/kg nimodipine increased by less than 2-fold the AMP dose necessary to induce AMP-appropriate responses. Higher doses of nimodipine combined with AMP did not increase the magnitude of this effect. Nimodipine enhanced the effects of AMP on response rate. Haloperidol (0.125 mg/kg) increased by approximately 4-fold, whereas diazepam (0.5 or 1.0 mg/kg) and morphine (5.0 mg/kg) increased by approximately 2-fold the AMP dose necessary to induce AMP-appropriate responses. The interaction with AMP was associated with enhanced reduction of response rate in the tests with diazepam and morphine but not haloperidol. These results suggest that nimodipine attenuates the DS properties of AMP, probably in a non-specific way, due to the ability of nimodipine itself to induce a discriminable internal state.

Stimulus properties of d-amphetamine as compared to 1-amphetamine

Rats were trained to discriminate between d-amphetamine and saline. The discriminable ED 50 values for amphetamine isomers were calculated from dose-response curves and the potency ratio was 4.9. Co-administration of the ED 50 S was shown to produce synergistic effects suggesting that the amphetamine isomers may share a common site of action.