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

Abstract

Repeated administration of CNS stimulants such as amphetamines and cocaine induces behavioural sensitization which can be influenced by the animal's environment. This study has evaluated the effect of restraint on the development and maintenance of ambulatory sensitization to methamphetamine and cocaine in mice. Subcutaneous administration of the CNS stimulants methamphetamine (2 mg kg(-1)) and cocaine (20 mg kg(-1)) seven times at three-day intervals resulted in ambulatory sensitization when the mice were placed in 20-cm diameter activity cages after each dose of the drug. However, if methamphetamine or cocaine was administered when the mice were in small jars (6-cm diameter) in which expression of ambulation, but not of circling and rearing, was completely restricted, the development of ambulatory sensitization was retarded or inhibited, with circling behaviour concurrently increased, when subsequent repeated doses of the drug were administered in the activity cage. Subsequent repeated treatment of ambulatory-sensitized mice with the drug or saline when the mice were in the jars did not change the levels of the ambulatory sensitization or the circling behaviour. These results suggest that the mice are sensitized to the behavioural effect of CNS stimulants which can be expressed in the environment in which the drug is administered. It is also considered that the established sensitization is strongly retained and is responsible for retardation or suppression of the development of sensitization to other behavioural stimulant effects.

Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption

“…Sensitization can be remarkably persistent (Paulson et al 1991; Lessov and Phillips 1998; De Vries et al 1998; Boileau et al 2006; Boehm et al 2008). It is reflected in behaviors like increased stereotypy (Ellinwood and Balster 1974; Camp et al 1994; Ferrario et al 2005) and locomotor stimulation (Post and Rose 1976; Kuribara 1998; Meyer and Phillips 2007; Kelly et al 2008), but can also be measured as an escalation in a neurochemical response (Pierce et al 1996; Vezina 2004). Changes in physical attributes of neurons with repeated drug exposure have also been seen (Ferrario et al 2005).…”