Adolescent Neurodevelopment

AbstractPurposeThe purpose of this article is to outline notable alterations occurring in the adolescent brain, and to consider potential ramifications of these developmental transformations for public policy and programs involving adolescents.MethodsDevelopmental changes in the adolescent brain obtained from human imaging work are reviewed, along with results of basic science studies.ResultsAdolescent brain transformations include both progressive and regressive changes that are regionally specific and serve to refine brain functional connectivity. Along with still-maturing inhibitory control systems that can be overcome under emotional circumstances, the adolescent brain is associated with sometimes elevated activation of reward-relevant brain regions, whereas sensitivity to aversive stimuli may be attenuated. At this time, the developmental shift from greater brain plasticity early in life to the relative stability of the mature brain is still tilted more toward plasticity than seen in adulthood, perhaps providing an opportunity for some experience-influenced sculpting of the adolescent brain.ConclusionsNormal developmental transformations in brain reward/aversive systems, areas critical for inhibitory control, and regions activated by emotional, exciting, and stressful stimuli may promote some normative degree of adolescent risk taking. These findings have a number of potential implications for public policies and programs focused on adolescent health and well-being

Low Dose Effects in Psychopharmacology: Ontogenetic Considerations

Low doses of psychoactive drugs often elicit a behavioral profile opposite to that observed following administration of more substantial doses. Our laboratory has observed that these effects are often age-specific in rats. For instance, whereas moderate to high doses of the dopamine agonist apomorphine increase locomotion, suppressed locomotor activity is seen following low dose exposure, with this low dose effect not emerging consistently until adolescence. A somewhat earlier emergence of a low dose “paradoxical” effect is seen with the 5HT1a receptor agonist, 8-OH-DPAT, with late preweanling, but not neonatal, rats showing increases in ingestive behavior at low doses but suppression at higher doses. In contrast to these ontogenetic increases in expression of low dose drug effects, low dose facilitation of social behavior is seen following ethanol only in adolescent rats and not their mature counterparts, although suppression of social interactions at higher doses is seen at both ages. This hormesis-like low dose stimulation appears related in part to overcompensation, with brief social suppression preceding the subsequent stimulation response, and also bears a number of ontogenetic similarities to acute tolerance, a well characterized, rapidly emerging adaptation to ethanol. Implications of these and other ontogenetic findings for studies of hormesis are discussed

5HT1A, 5HT1B and 5HT2 Receptor Agonists Induce Differential Behavioral Responses in Neonatal Rat Pups

Sprague-Dawley rat pups at 3–4 days prenatally were tested in both the absence and presence of milk following administration of various doses of either the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), the 5-HT1B agonist 1-(3-chlorophenyl)piperazine (mCPP), or the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Administration of 8-OHDPAT decreased mouthing, increased probing and increased behavioral activation. Conversely, the 5-HT2 agonist DOI and the 5-HT1Bagonist mCPP increased mouthing and decreased probing. mCPP and DOI differed in their effects on behavioral activation, with mCPP decreasing and DOI increasing this composite behavioral score. mCPP increased grooming, whereas DOI elicited a characteristic unusual positioning of the limbs. Thus it appears that 5-HT1A, 5-HT1B and 5-HT2 receptor subtypes are present in the neonate and elicit differential behavioral responses upon stimulation with selective agonists. Ontogenetic variations in the balance among these receptor subtypes during development may be related to the ontogenetic reversal that has been previously reported in the impact of serotonin manipulations on mouthing and suckling behavior during the neonatal to weanling age period

Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats

The dynorphin/kappa opioid receptor (DYN/KOR) system has been identified as a primary target of stress due to behavioral effects, such as dysphoria, aversion, and anxiety-like alterations that result from activation of this system. Numerous adaptations in the DYN/KOR system have also been identified in response to stress. However, whereas most studies examining the function of the DYN/KOR system have been conducted in adult rodents, there is growing evidence suggesting that this system is ontogenetically regulated. Likewise, the outcome of exposure to stress also differs across ontogeny. Based on these developmental similarities, the objective of this study was to systematically test effects of a selective KOR agonist, U-62066, on various aspects of social behavior across ontogeny in non-stressed male and female rats as well as in males and females with a prior history of repeated exposure to restraint (90 min/day, 5 exposures). We found that the social consequences of repeated restraint differed as a function of age: juvenile stress produced substantial increases in play fighting, whereas adolescent and adult stress resulted in decreases in social investigation and social preference. The KOR agonist U-62066 dose-dependently reduced social behaviors in non-stressed adults, producing social avoidance at the highest dose tested, while younger animals displayed reduced sensitivity to this socially suppressing effect of U-62066. Interestingly, in stressed animals, the socially suppressing effects of the KOR agonist were blunted at all ages, with juveniles and adolescents exhibiting increased social preference in response to certain doses of U-62066. Taken together, these findings support the hypothesis that the DYN/KOR system changes with age and differentially responds and adapts to stress across development. Keywords: Juvenile, Adolescent, Adult, Social behavior, Kappa opioid receptor, Restraint stress, Developmen