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

Abstract

Mice given five repeated administrations of methamphetamine (MAP: 2 mg/kg SC) or cocaine (COC: 20 mg/kg SC) at 3-day intervals in a round tilting-type activity cage (20 cm in diameter) showed sensitization to the ambulation-increasing effect of each drug. The mean 3- or 2-h overall activity count at the fifth administration of MAP or COC, respectively, was 2.3-2.5 times higher than that at the first administration. Mice given MAP or COC 4 times in round spaces (15-30 cm in diameter), where the floor did not tilt, exhibited sensitization as strong as that demonstrated by mice given each drug in the activity cages, when the mice were given the fifth administration in the activity cages. In contrast, mice repeatedly given the drugs in spaces 4-9 cm in diameter never, and those in space 12 cm in diameter only partially, exhibited sensitization to MAP and COC. Furthermore, mice given MAP or COC 4 times in their home cages (25D x 20W x 15H cm, with ten mice in each cage) showed partial sensitization. Repeated administration of saline to mice in activity cages, in the spaces 4-30 cm in diameter, or in the home cages did not cause significant change in the sensitivity to either MAP or COC. These results suggest that repeated experience of the stimulant effect of drug and the resultant ambulation is required for induction of sensitization to MAP and COC in terms of ambulation in mice. It is also suggested that spaces larger than 12 cm in diameter, which correspond to 2-2.5 times as long as the body length without tail, and no interference from other mice are required for induction of strong sensitization to both MAP and COC.

Importance of Initial Environments in the Development of Ambulatory Sensitization to Methamphetamine and Cocaine in Mice

“…These experiments have revealed that sensitization to the ambulation-increasing effect of methamphetamine and cocaine was established by the fourth administration and that almost the same level of ambulatory sensitization was reproduced thereafter when the mice were exposed to the activity cages after each administration of the drug. These results are consistent with those obtained from previous studies (Kuribara 1995(Kuribara , 1996b(Kuribara , 1997. However, when mice were first exposed to small jars, in which the expression of ambulation was selectively restricted, two to three times after administration of methamphetamine or cocaine, ambulatory sensitization was significantly retarded or reduced during subsequent repeated administration of drug in the activity cages, despite administration a sufficient number of times (4-6) for the development of maximum ambulatory sensitization (as demonstrated for groups M1 and Cl).…”

“…Methamphetamine HCl (Dainippon, Osaka, Japan) and cocaine HC1 (Takeda, Osaka, Japan) were dissolved in physiological saline and administered subcutaneously in a constant volume of 0.1 mL per 10 g. The doses of methamphetamine (2 mg kg-' in the salt form) and cocaine (20 mg kg-' in the salt form) were optimum for induction of the ambulatory sensitization without producing strong stereotypies (Kuribara 1996b).…”

“…Thus, the sensitization to the CNS stimulant is manifested as behaviour which can be expressed in the environment in which the experiment is performed (Segal 1975;Willner et a1 1992;Martin-Iverson & Fawcett 1996). Hirabayashi & Alam (1981), Hirabayashi et a1 (1991) and Kuribara (1995Kuribara ( , 1996bKuribara ( , 1997 demonstrated that mice did not show ambulatory sensitization when they were kept in a small jar (less than 9 cm in diameter) for 3 and 2 h after each administration of methamphetamine and cocaine, respectively, to restrict the expression of ambulation without inhibiting either vertical movement or turning. These results suggest two possibilities: either the mice acquire sensitization to behaviour other than ambulation during the repeated administration of the CNS stimulant when in the jars, or the established sensitization might be retained for a long period and can act to inhibit or retard the induction of sensitization to other behaviour during subsequent repeated administration.…”

Sensitization to the Motor Stimulant Effects of 3,4-Methylenedioxypyrovalerone (MDPV) and Cross-Sensitization to Methamphetamine in Rats

“…The reasons for these observations are unknown, but we do not believe this influenced the results, as previous work has revealed that intermittent drug administration with longer inter-dose intervals (e.g. 48 hrs or longer) produces greater locomotor sensitization for methamphetamine, cocaine, and morphine [26,32,33]. As mentioned above, it has recently been demonstrated that MDPV-induced hyperactivity is positively correlated with plasma MDPV levels, but inversely related to plasma levels of the MDPV metabolites 3,4-dihydroxypyrovalerone and 4-hydroxy-3-methoxypyrovalerone [4].…”

The Myth of Panic Spontaneity: Consideration of Behavioral and Neurochemical Sensitization

“…Exacerbation of panic symptoms might be occasioned by recurrent stressors, panic experience and/or cues associated with such stimuli. In this regard, panic profiles may parallel nonhuman instances of sensitization while comorbid psychological disorders, including depression may outline the variable contributions of experiential and organismic factors [48], including gender susceptibility [49][50][51][52][53][54][55][56] as well as environmental context and conditioning [57][58][59][60][61][62] to the expression of pathological states. Parametric analyses reveal variability in the induction, persistence and magnitude of effects relative to the behavior examined and the brain sites involved.…”