Comparison of Sensitization to Ambulation-increasing Effects of Cocaine and Methamphetamine after Repeated Administration in Mice

Abstract

The effects of repeated (5 times) subcutaneous administration of cocaine (10, 20 or 40 mg kg-1) and methamphetamine (1, 2 or 4 mg kg-1) at 3-4 day intervals have been compared in mice placed individually into tilting activity cages. A progressive enhancement of the ambulation-increasing effect was noted for 3-4 h after each administration, indicating that sensitization occurred. This occurrence and the existence of an optimal dose producing sensitization were similar for both drugs. However, enhancement of the effect after cocaine progressed rapidly and maximum sensitization was observed earlier than after methamphetamine administration. Moreover, the higher doses of cocaine (40 mg kg-1) caused stereotypies concurrent with preconvulsive signs of short duration that were enhanced by serial administration. In contrast, methamphetamine caused a more progressive enhancement, but stereotypies with no preconvulsive signs were produced by the higher dose (4 mg kg-1). The respectively, effective doses for the development of enhancement suggested that cocaine was less potent than methamphetamine in producing sensitization. Cross-sensitization occurred between both drugs. Thus, sensitization to cocaine was distinct from that to methamphetamine due to differences in its rapidity, intensity, and the presence or absence of preconvulsive changes.

Importance of post-drug environmental factors for induction of sensitization to the ambulation-increasing effects of methamphetamine and cocaine in mice

“…However, the mice given either MAP or COC in spaces 4-9 cm did not show any sensitization to the ambulation-increasing effect of individual drugs at the challenge administration, and the activity counts were almost the same as those given saline in the pretreatment phase. These results are in agreement with previous reports that mice given ten repeated administrations of MAP (Hirabayashi and Alam 1981) or COC (Hirabayashi et al 1991) in glass jars (6 cm in diameter, and 15 cm in height) at l-7-day intervals did not exhibit sensitization. On the other hand, putting the mice in spaces 15 cm in diameter or larger did not affect the induction of sensitization to both MAP and COC.…”

“…Sensitization to the ambulation (locomotion)-increasing effect of methamphetamine (MAP) (Hirabayashi and Alam 1981) or COC (Hirabayashi et al 1991) was not induced when the mouse was kept in a glass jar (6 cm in diameter and 15 cm in height) during the acute stimulant effect of the drug. In such a space, the mouse was restricted in terms of ambulation, but not turning and vertical movements, suggesting that repeated experience of the acute stimulant effect of drug and the resultant ambulation is one important factor for induction of sensitization to MAP and COC in terms of ambulation in mice.…”

Repeated exposure to inhaled toluene induces behavioral and neurochemical cross-sensitization to cocaine in rats

“…These results are the first to demonstrate a cross-sensitization between toluene and cocaine and are consistent with the ability of toluene to enhance apomorphine-induced increases in locomotor activity (von Euler et al 1991(von Euler et al , 1993. Also, these results are consistent with previous findings that other drugs of abuse (e.g., amphetamine, morphine and caffeine) produce cross-sensitization with cocaine (Kazahaya et al 1989;Lett 1989;Akimoto et al 1990;Hirabayashi et al 1991;Horger et al 1991).…”

Clorgyline-induced switch from locomotion to mouthing in sensitization to the dopamine D2/D3 agonist quinpirole in rats: role of sigma and imidazoline I2 receptors

“…Chronic administration of the dopamine agonists amphetamine, cocaine, apomorphine, bromocriptine, and quinpirole (QNP) results in a progressive augmentation of the motor response to these drugs (Segal and Schuckit 1983;Mattingly and Gotsick 1989;Hirabayshi et al 1991;Hoffman and Wise 1992;Szechtman et al 1994b). This phenomenon, termed behavioral sensitization (Robinson and Becker 1986), has received considerable attention as a potential experimental model for several psychopathological states in humans, including schizophrenia, obsessive-compulsive disorder and addiction (Angrist 1983;Robinson and Berridge 1993;Szechtman et al 1999).…”