Cocaine-induced behavioral sensitization in the young rat

Abstract

Rationale: Repeated psychostimulant treatment has been shown to sensitize the locomotor activity of young rats, but there is conflicting evidence suggesting that this sensitized response will persist across only a few drug abstinence days. Objective: The purpose of the present study was to determine whether: (a) young rats are capable of expressing a sensitized locomotor response after an extended drug abstinence period, and (b) the longevity of the sensitized response is critically affected by either the number of drug pretreatment days or environmental conditioning factors. Methods: Young rats were pretreated with saline or cocaine (15 mg/kg or 30 mg/kg, i.p.) for either five or ten consecutive days [i.e., on postnatal days (PD) 16-20 or PD 11-20]. After each daily injection, rats were placed in activity chambers, and locomotion was measured for 30 min. To assess environmental conditioning factors, some rats were injected with saline prior to being placed in the activity chambers and then injected with cocaine prior to being returned to the home cage. After one or seven abstinence days (i.e., on PD 22 or PD 28), rats received a challenge injection of saline or cocaine (15 mg/kg) in the activity chamber and locomotion was assessed. Results: Young rats exhibit cocaine-induced locomotor sensitization after either a short (1-day) or long (7-day) drug abstinence period. When a long abstinence period was used, locomotor sensitization was only apparent when cocaine pretreatment lasted for 10 days. Conditioning factors were also important for determining whether locomotor sensitization was expressed, because young rats pretreated with cocaine in the home cage did not show a sensitized locomotor response after seven abstinence days. Conclusions: Young rats are capable of showing cocaine-induced locomotor sensitization after an extended abstinence period. Both the number of drug pretreatment days and the environmental context in which cocaine was given (i.e., the activity chamber or home cage) influenced the longevity of cocaine-induced locomotor sensitization.

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

“…Sensitization of psychomotor activation has been more reliably reported with drugs other than alcohol, including cocaine (Pecins- Thompson and Peris, 1993;Mattingly et al, 1994;Schenk and Partridge, 2000;Zavala et al, 2000;Erb et al, 2003;Haile et al, 2003;Matell et al, 2004), amphetamine (Robinson, 1984;Paulson and Robinson, 1991;Serwatkiewicz et al, 2000;Vezina and Queen, 2000;Crombag et al, 2001;Fukami et al, 2004), and opiates (Balcells-Olivero and Vezina, 1997;Ojanen et al, 2005).…”

Enhanced Reactivity and Vulnerability to Cocaine Following Methylphenidate Treatment in Adolescent Rats

“…Ontogenetic studies indicate that after cocaine treatment during pre-weanling (Zavala et al 2000;Wood et al 1998), post-weanling (Ujike et al 1995) and peri-adolescent periods (Laviola et al 1995), rats develop an enhanced behavioral response to cocaine. Unlike previous studies (Laviola et al 1995), we observed increasing sensitization to the locomotor stimulant effects of cocaine over time.…”

“…Sensitization seems to occur only when the sensitizing regimen is restricted to late pre-weanling life or later and when repeated drug exposure is paired with the testing chamber or when long pretreatment regimens are used. Sensitization may be limited to short treatment-to-test intervals (McDougall et al 1994;Tirelli and Ferrara 1997;Wood et al 1998) although other studies indicate persistent sensitization Zavala et al 2000).…”

“…Accordingly, critical questions about treatment of ADHD with psychostimulants are: do children and adolescents sensitize during repeated drug exposure and, if so, does sensitization persist? Unfortunately, animal studies have provided conflicting answers (Laviola et al 1995;Ujike et al 1995;Snyder et al 1998;Wood et al 1998;Izenwasser et al 1999;McDougall et al 1999;Zavala et al 2000). Sensitization to MP in rodent models has been well documented (Shuster et al 1982;Gaytan et al 1997;Crawford et al 1998; but see McNamara et al 1993), but the use of relatively high doses in most studies, and the apparent inability of MP to induce long-term locomotor sensitization in young animals (McDougall et al 1999), has raised questions regarding the clinical relevance of such findings (National Institute of Mental Health 1999).…”

Behavioral responses during the initial exposures to a low dose of cocaine in late preweanling and adult rats

“…injections [18,40,72,82,83]. In additional studies, multiple doses of stimulants were administered to preweanling or adolescent animals, but those studies examined the effects of the long-term expression of sensitization either later in adolescence [58,68,72] or in adulthood [72].…”