Behavioral and Neurochemical Responses to Cocaine in Periadolescent and Adult Rats

Abstract

Although recreational drug use by human adolescents is a well-known and long-standing problem, relatively little is known regarding differences in behavioral and physiological responses to abused substances in adolescent vs adult animals. The present study compared effects of the psychomotor stimulant, cocaine, in periadolescent (postnatal days 37-52) and adult (postnatal days 75-90) male Wistar rats. Locomotion and motor stereotypy were recorded after acute and repeated cocaine injections (0, 10, or 20 mg/kg cocaine, intraperitoneal (i.p.), four injections spaced 5 days apart). Spontaneous acquisition of intravenous (i.v.) cocaine self-administration was investigated in two dose groups (B0.37 or 0.74 mg/kg/infusion) over 14 days. Dopamine levels in the nucleus accumbens were recorded under basal conditions (no net flux method) and after cocaine administration (B0.37, 0.74, and 2.92 mg/kg/i.v. infusion or 20 mg/kg i.p.) using in vivo microdialysis. The locomotor data are in partial agreement with previous reports of hyposensitivity to acute cocaine in periadolescent vs adult rats; periadolescents were less active overall than adults. Moreover, adult rats exhibited significant locomotor sensitization after repeated injection of 10 mg/kg cocaine, whereas periadolescents required the high dose of 20 mg/kg cocaine to demonstrate sensitization. Neither age group showed sensitization of motor stereotypies. No age-related difference was observed in acquisition of cocaine self-administration, or in basal or cocaine-stimulated nucleus accumbens dopamine. These experiments imply a developmental dissociation between the motor activating and reinforcing effects of cocaine. Similarities in dopamine levels across age groups suggest that age-specific motor responses to cocaine are not mediated by dopamine in the nucleus accumbens. Neuropsychopharmacology (2007) 32, 625-637.

Protracted ‘Pro-Addictive’ Phenotype Produced in Mice by Pre-Adolescent Phenylpropanolamine

“…However, two major lines of evidence argue against a direct relationship between the protracted effects of juvenile PPA exposure and the locomotor-and catecholamine-sensitizing effects of cocaine. For one, the locomotor-activating or -sensitizing effects of psychomotor stimulants can be dissociated from the ability of this drug class to elevate extracellular levels of dopamine and norepinephrine in the NAC (eg, Frantz et al, 2006;Ito et al, 2006;Szumlinski et al, 2000aSzumlinski et al, , b, 2004bSzumlinski et al, , 2005bZhang et al, 2006). These observations are supported by the present finding that despite reducing the capacity of acute cocaine to elevate NAC levels of dopamine and norepinephrine, PPA pretreatment did not alter the acute motor-stimulatory effects of cocaine.…”

Low dose nicotine treatment during early adolescence increases subsequent cocaine reward

“…Other studies with naive acquisition in both adolescents and adults show a similar lack of dose effect in this early phase [26,27]. However, a cocaine dose-effect in responding is not necessary to show enhanced sensitivity, especially since both doses used are considered to be low.…”

“…Such epidemiological findings suggest that adolescents may be less sensitive to the rewarding effects of cocaine than adults. Although recent animal studies have not supported this conclusion [12,26], these studies have involved the administration of cocaine over a period of several days. In our self-administration paradigm, in which nose-pokes are used instead of levers, a significant proportion of animals acquire selfadministration on the first day of testing.…”

“…The significant main or interaction effects were further analyzed by one-way ANOVA with Dunnett's-adjusted post hoc comparisons. Criteria for self-administration were established as twelve reinforced responses over the two hour test session with a minimum 2:1 ratio of reinforced to non-reinforced responding [26]. The percentage of animals reaching criterion in each group on the first and fifth testing days were compared by χ 2 analysis ( Figure 1C).…”

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

“…The adolescent period in rodents is typically estimated to span postnatal (P) days 28-42 (Spear and Brake, 1983); however, other estimates have extended the age range to include up to postnatal day 55 (Spear, 2000;Chen et al, 2007;Frantz et al, 2007). Adolescent rats share many behavioral and neurobiological characteristics with human adolescents, and have been useful in determining factors contributing to vulnerability to drugs, including nicotine, during this ontogenetic period (Spear, 2000).…”