Periadolescence: Age‐dependent behavior and psychopharmacological responsivity in rats

Abstract

The behavior and psychopharmacological sensitivity of periadolescent rats are examined in this review. Periadolescent rats are hyperactive and engage in more conspecific play behavior than younger or older rats. When compared with other-aged rats, periadolescents exhibit enhanced performance in simple active-avoidance learning tasks, but perform poorly in more complex appetitive and avoidance learning tasks in which increases in locomotor activity do not improve performance, perhaps as a result of age-specific alterations in selective attention or stimulus processing. Such behavioral "anomalies" of periadolescent animals observed in traditional laboratory situations may be in some way adaptive when considered in the context of the animals' natural habitat. In terms of psychopharmacological responsiveness, periadolescent rats, when compared with younger or older animals, are less sensitive to catecholaminergic agonists but are more responsive to the catecholaminergic antagonist haloperidol. This pattern of psychopharmacological sensitivity suggests that the catecholaminergic systems may be temporarily hyposensitive during the periadolescent period. Evidence is presented that a negative feedback system in the form of dopamine autoreceptors may become functionally mature in mesolimbic brain regions during the periadolescent period. The possibility is presented that maturation of these self-inhibitory autoreceptors might result in a temporary decrease in the efficacy of mesolimbic dopamine projections, perhaps contributing to the psychopharmacological and behavioral characteristics of periadolescent animals. In support of this suggestion, evidence is reviewed indicating that the behavior of adult animals with lesions of the ventral tegmental area, a region containing cell bodies from which these mesolimbic dopaminergic projections originate, resembles that of periadolescent rats.

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).…”

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

“…In our hands, the repeated administration of saline to adult mice typically induces either no change, but more often, a reduction in locomotion across injections, indicative of habituation to the environment, handling, and injection procedures (see Figure 2b; Szumlinski et al, 2002Szumlinski et al, , 2004aSzumlinski et al, , 2005a. Whether the change in locomotor behavior of saline controls reflected an age-dependent general increase in locomotor hyperactivity (eg, Niculescu et al, 2005;Spear and Brake, 1983) or a sensitized response to the injection stressor cannot be discerned by the results of the present study. However, in support of the latter possibility, the locomotor response to an acute saline injection does not differ between mice aged 21 and 28 days (Guerriero et al, 2006).…”

“…For each experiment, pups from three different litters were weaned on postnatal day (PND) 21 and housed in same-sex pairs in brown, clear standard polyethylene cages (15 cm wide  23 cm long  16 cm high) with woodchip bedding, under a regular 12-h light cycle (lights on 0700 hours). Between PND 21 and 30, a time corresponding to preadolescence in rodents (Adriani et al, 2004;Cirulli and Laviola, 2000;Spear and Brake, 1983), pups were administered, once daily, intraperitoneal (i.p.) injection of either saline vehicle (vol ¼ 0.01 ml/g) or 5, 10, and 40 mg/kg PPA.…”

“…Although sympathomimetic drugs can exert psychomotor-activating effects (eg, Eisenberg et al, 1987;Miller et al, 1999;Mittleman et al, 1993), earlier reports for PPA conducted in adult rats failed to observe hyperactivity in response to systemic injections of PPA (Eisenberg et al, 1987;Mittleman et al, 1993). As spontaneous locomotion, as well as drug-induced changes in motor hyperactivity, can depend upon the age of animal (eg, Bolanos et al, 1998;Carlezon and Konradi, 2004;Dafny and Yang, 2006;Niculescu et al, 2005;Spear and Brake, 1983), we examined for changes in the locomotor activity of juvenile mice in response to repeated PPA administration. Consistent with earlier reports for the locomotor effects of PPA in adult rats (Eisenberg et al, 1987;Mittleman et al, 1993), PPA administration to juvenile mice did not elicit motor hyperactivity, but rather suppressed locomotion in a doseindependent manner, relative to saline controls (Figure 1b).…”

Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex

“…In the rat, adolescence is considered to last from postnatal days 21-28 till postnatal days 42-59 (depending on the authors; (Spear, 2000;Spear & Brake, 1983;Tirelli, Laviola, & Adriani, 2003)). A number of animal models have been developed to study the short and long-term impact of stress during adolescence (Isgor, Kabbaj, Akil, & Watson, 2004;Ito, Nagano, Suzuki, & Murakoshi, 2010;McCormick, Smith, & Mathews, 2008;Sterlemann et al, 2010;Toledo-Rodriguez & Sandi, 2011) and during the juvenile period (Avital & Richter-Levin, 2005;Jacobson-Pick & Richter-Levin, 2010).…”