Duration of sensitization to the locomotor stimulant effects of ethanol in mice

Abstract

Behavioral sensitization to the psychomotor stimulant effects of some drugs can be quite persistent, lasting for weeks to months after cessation of drug exposure. We investigated the duration of sensitization to the locomotor stimulant effects of 2.0 g/kg ethanol (EtOH) and determined whether repeated EtOH administration would lead to alterations in blood EtOH clearance rates. Female mice were injected (IP) daily for up to 10 consecutive days with saline or EtOH. Baseline activity and acute EtOH locomotor responses were evaluated in Omnitech automated activity monitors (10-min test), with horizontal distance traveled as the measure of locomotion. Locomotor activity response to EtOH was reevaluated immediately after the final daily EtOH injection, and at 5-day intervals during which no EtOH was administered. Tail blood samples for determination of blood ethanol concentrations (BECs) were collected from EtOH-treated mice at the end of activity sessions. Sensitization lasted for up to 29 days, and in two of three of the behavioral sensitization studies, repeated EtOH treatment resulted in elevated BECs. There was no significant effect of repeated EtOH exposure on EtOH clearance rate in a study involving no behavioral testing. The demonstration of persistent behavioral sensitization may imply a lasting hypersensitivity of certain neural pathways to EtOH, thus increasing the reinforcing value of EtOH and the probability of relapse to EtOH drinking after abstinence.

The Role of Opioid Receptor Subtypes in the Development of Behavioral Sensitization to Ethanol

“…This effect increased progressively across the sessions and ended up reaching a plateau, indicating that our protocol led to the development of a ceiling effect on the locomotor stimulation produced by repeated ethanol administration. The sensitized response to ethanol was also evident when mice were tested following an abstinence period of 7 days, suggesting, as previously reported (Lessov and Phillips, 1998), persistent neural changes induced by ethanol. Interestingly, it has been postulated that such persistence could be associated with potentially permanent adaptations in neural pathways important for the motivational properties of drugs of abuse (Kalivas et al, 1993;Robinson and Berridge, 1993).…”

Does context influence the duration of locomotor sensitization to ethanol in female DBA/2J mice?

“…Lessov and Phillips (1998) undertook similar experiments and concluded that ethanol sensitization in mice persists for up to 23 days although there was some disagreement among individual experiments within the larger study; whereas one experiment suggested that ethanolinduced locomotor sensitization lasted for at least 23 days, another suggested that it may dissipate by day 17. In a more recent study Fish et al (2002) demonstrated continued ethanol sensitization persisting out to post-sensitization day 58.…”

“…Although we were interested in only a limited number of group comparisons, we recognized that Statistica would perform Newman-Keuls post-hoc tests for every possible comparison following the significant interaction of treatment and day. Because this approach would unnecessarily restrict alpha to an ever greater extent with the inclusion of each additional induction day (in an effort to control family-wise error), an priori decision was made to separately compare each of the daily activity scores of the RE-RS-E group to its own activity scores on days 2 or 3, each of the daily activity scores of the RS-RE-E group to its own activity scores on day 3, and each of the experimental groups (RE-RS-E and RS-RE-E) to the control group (RS-RS-E) on each induction day (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). When the locomotor activity of the RE-RS-E mice was compared using this approach they exhibited a significant acute locomotor stimulant effect on day 3 (compared to day 2, p < 0.01; compared to the RS-RS-E control group on the same day, p < 0.05), as well as an enhancement of this effect when compared to the activity scores of the RS-RS-E controls on days 3 and 5-13 (p's < 0.05).…”

“…For example, little is known about the persistence of ethanol sensitization in mice, and the identification of possible neuroadaptive processes that might underlie the behavioral phenomenon has proven difficult. Lessov and Phillips (1998) demonstrated that sensitization may last for up to 23 days in female mice from an out bred mouse population (originating from the HS/Ibg heterogeneous mouse stock). However, several slightly different variations on the experiment did not arrive at a common conclusion, a result the authors attributed to the inherent genetic variability of the out bred mouse population, and no other genetic mouse populations were examined.…”

Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse

“…2;2005a). These are not unlike procedures most conducive to the induction of the psychomotor activating effects of alcohol, where repeated and spaced injections of alcohol (i.e., intermittent schedules of alcohol exposures), induce stronger psychomotor activating effects than in controls provided with massed exposures to alcohol (Pecins- Thompson and Peris, 1993;Lessov and Phillips, 1998;Quadros et al, 2003). Similarly, other abused drugs induce psychomotor activation effects (Robinson, 1984;Wise and Bozarth, 1987;Wise and Rompre, 1989) that are exaggerated by repeated and spaced exposures to the drug, relative to controls receiving fewer but massed exposure to similar amounts of the drug (Salamone, 1992;Stewart, 2003).…”