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

Abstract

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.

The discriminative stimulus effects of midazolam are resistant to modulation by morphine, amphetamine, dizocilpine, and γ-butyrolactone in rhesus monkeys

“…Whereas benzodiazepines seem to enhance the effects of opioids, they attenuate some effects of amphetamines or cocaine and are often used by polydrug abusers to diminish unwanted effects that emerge as abusers discontinue an episode of stimulant use (Degenhardt and Topp 2003; Gelkopf et al 1999). Although attenuation of the discriminative stimulus effects of amphetamine and cocaine by benzodiazepines has been reported (Barrett et al 2005; Druhan et al 1991; Goeders et al 1993; Negus et al 2000; Nencini and Woolverton 1988), amphetamine did not alter the discriminative stimulus effects of midazolam in the current study. These asymmetrical interactions between amphetamine and benzodiazepines in drug discrimination studies suggest that increased use of benzodiazepines in stimulant abusers is related to alterations of effects of stimulants by benzodiazepines but not vice versa.…”

The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

“…However, the specificity of these effects to the dopamine releasing ability of amphetamine is questionable; the effects seen by Grebb (1986) occurred at doses higher than those we have used and are possibly due to other effects of calcium antagonists that are seen at high doses (De Feudis, 1987). Nencini & Woolverton (1988) have recently demonstrated that nimodipine weakly inhibited the discriminative stimulus effects of amphetamine, but considered this to be a non-specific effect as it was not dose-related, of small magnitude and associated with a significant reduction in response rate. Our results are more clearcut in that neither nifedipine nor Bay K 8644 had an effect on the discrimination performance by rats, although both reduced the response rate.…”

Effects of nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine in humans

“…Further studies of the effects of calcium channel modulators on cocaine discrimination in laboratory animals similar to those carried out with amphetamine (Nencini and Woolverton 1988) might address whether dihydropyridine calcium modulators attenuate the reinforcing or discriminative stimulus properties of cocaine. Human studies of other dihydropyridines such as nimodipine, a calcium channel blocker with more selective central nervous system effects (Freedman and Waters 1987), and additional dose response studies with nifedipine and cocaine are necessary to assess the general applicability of our results to problems of cocaine abuse in humans.…”