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Complex Behaviors

A Rodent Model for Human Adolescence

By July 4, 2019No Comments


Adolescence is for all of us, a very important and defining period of our lives. It is overall defined as the transitional period in which the further development of the reproductive system occurs and in which individuals acquire new survival skills that allow for independence of parental care.[1] However, the definition seems to vary according to the field of study describing the period, as the transition incorporates cognitive, psychological, social, as well as behavioral development. For example, cognitively, it is a period in which the brain is undergoing many complex changes, e.g. changes in dopamine receptor density, that will have a long-term impact on decision-making and cognitive processes. From a behavioral standpoint, adolescence is a time of high-risk behavior, impulsivity, and exploration. Adolescence is also a time marked with higher probability to initiate drugs and with increased vulnerability of developing addictions that would last well into adulthood. [2][3]

One difficulty in studying adolescence is defining the borders of the period. Often, adolescence is mistaken for puberty due to the overlapping of both concepts, however, the two are not interchangeable.[3] Puberty can be exactly defined in physiological terms, starting with the onset of increased nocturnal secretion of gonadotropin-releasing hormone (GnRH) towards the end of the first decade of life.[4] Adolescence, however, also includes psychological and social factors, and is a lot hard to define precisely. Two behavioral factors that can indicate transition from childhood into adolescence are changes in the hormonal state, with the emergence of sexually oriented partner-seeking behaviors and elevated levels of social, affiliative and playful behavior.[3][11][12]

One hypothesis states that the exploratory behavioral profile of adolescents might motivate them towards the initiation of drugs i.e. firstly, easily accessible drugs like alcohol, marijuana, and tobacco, and later, psychostimulants and opiates. In other words, these sensations- and novelty-seeking behavioral traits may explain the elevated curiosity and the experimenting with psychoactive agents of human adolescents.[3]

Due to the many and peculiar aspects of adolescence mentioned above, it is important to get a better understanding of this essential, vulnerable and highly transitional period in time. That is why the interest in relevant animal models that can be used for studying the underlying behavioral, neurobiological and neuroendocrine changes that happen in adolescence has increased in recent decades.

Rodent model for adolescence

In rodents, adolescence is typically defined as the entire postnatal period ranging from weaning (postnatal day (PND) 21) to adulthood (PND 60). In more detail, the period can be divided into three age-intervals, namely early adolescence (prepubescent or juvenile, PND 21 – 34), middle adolescence (peri-adolescent, PND 34 – 46), and late adolescence (young adult, PND 46 – 59).[3] In particular, periadolescent rodents have been proven to be a useful model for studying behavioral disorders in adolescence, including drug abuse, schizophrenia, and attention- deficit-hyperactivity disorder (ADHD).[1] The validity of the model for the purpose of comparison or extrapolation to the human case has been endorsed by many researchers.[1][3][5–7]

Periadolescents are generally hyperactive and indulge in affiliative and playful behavior, which expresses itself in increased grooming. Overall, they exhibit increased novelty seeking behavior paired with decreased novelty-induced stress and anxiety. In addition, they show enhanced risk-taking behavior, together with their more impulsive and restless behavior, compared to juveniles and adults. They show elevated basal levels of locomotor and exploratory activity. In summary, they exhibit a more unbalanced and ‘extremes-oriented’ behavior pattern than other age groups, which is very similar to human adolescent behavioral patterns.[2][3]

Interestingly, neurobiological studies have shown a temporary decrease in the functional efficacy of the mesolimbic dopamine projections in periadolescent rats. More specifically, they showed decreased basal dopamine release whilst having a larger dopamine storage pool. It is hypothesized that because of the lack of mesolimbic dopamine release adolescents show an important reduction in basal levels of motivation. However, due to their larger storage pools, adolescents are able to release much more dopamine when stimulated to the maximum extent by environmental and/or pharmacological stimuli.[3] Andersen et al. (2000) suggested a possible explanation for this phenomena: dopamine receptors are overexpressed prior to puberty and receptor density decreases thereafter, undergoing a type of synaptic pruning, as a function of maturing the neural circuitry.[7] The same goes for nicotine and acetylcholine receptors. This might explain the increased sensitivity to dopaminergic drugs and nicotine.[3]

Behavioral Assessment of Rodent model of Adolescence

There are various ways for testing the above mentioned behavioral traits of periadolescent rodents. In this part, the most important behavioral traits are listed together with the appropriate tests to study those behaviors.

Novelty seeking

Both rodent and human adolescents have been known to show high-risk behavior, which can result in the initiation of drugs. Testing novelty preference in rodents is an effective measure for high-risk taking behavior due to its strong correlation. High novelty-preference has been linked to higher sensitivity to psychomotor drugs, e.g. amphetamines and cocaine, as well as to higher probability of self-induction. In addition, high-novelty preferring rats show higher behavioral and neurochemical responses to environmental stressors.

A study conducted by Stanfield et al. (2004) compared novelty preference behavior in different age categories including adolescent and adult rats. Periadolescent rats were assessed in a playground maze test and an open field test. They showed that adolescents and adults both exhibit a preference for novelty but that variations of learning about the novel object can mask these tendencies differently (i.e. trials/exposure). More specifically, increasing the number of habituation trials (over approximately four trials) may decrease the preference for novelty. It has been hypothesized this might be due to adolescent rats overgeneralizing when they are repeatedly exposed to an environment and several objects.[2]

Risk-taking and exploratory behavior

Risk-taking and exploratory behavior is very closely related to novelty seeking behavior. Generally, adolescents have a stronger inner drive to explore and are thus prone to take more risks. It is easy to test these behaviors using the elevated plus-maze. Spatiotemporal (counts of open and closed arm entries) and behavioral parameters (rearing, head dipping, and stretched-attend postures) were scored in a study on adolescent and adult mice conducted by Macri et al. (2002).  Adolescent mice were shown to have a higher percentage of open arm-entries and reduced anxiety while exploring compared to adult mice. This indicates that adolescence can be characterized by an elevated drive towards the exploration of unknown environments regardless of the risk.[8]

Drug sensitivity

As mentioned before, compared to adults, adolescents have a higher probability of initiating and using soft as well as hard drugs. A clinical mouse study (Holliday et al. (2016)) looked at the effects of nicotine exposure during adolescence and found that it affected both cognition and emotional behavior when they grew into adulthood much more than it affected adults exposed to nicotine. More specifically, it impacted their contextual fear learning capability, depression-like behavior and their dendritic length of CA1 neurons in the hippocampus. These results were different when exposure occurred during adulthood. In this case, nicotine did not produce the same long-term impairments in contextual learning nor in depression-like behaviors. The long-term behavioral deficits seen in the mice that were exposed by nicotine during adolescence could be explained by the fact that there are structural changes in the dendritic arborization of pyramidal cells in CA1 sub-region of the hippocampus during that period. It is known that contextual fear learning is an hippocampal-dependent task, so deficit in this ability can be related to these structural changes. For testing fear learning, they used a contextual and cued fear conditioning paradigm, where freezing behaviors can be used as a measure of experienced fear. For depression-like behaviors, they used a forced swim test, with the latency for the mouse to become immobile used as a measure.[9]

Anxiety-like and aggressive-like behaviors

Adolescence is a critical time for the development of various cognitive functions, including executive function, excitatory/inhibitory balance,  synaptic stabilization, and synaptic pruning. Experiencing heightened stress and anxiety, due to early life stressors, for example, might have a negative impact on the development of these functions.

In 2010, Shin et al carried out a study on the effect of neonatal maternal separation in mice. They assessed anxiety-like behavior in the elevated plus maze and open field test. Adolescent mice, that were separated from their mother in early life exhibited anxiety-like behavior up till the third day of the trial. They also tested aggressive-like behaviors using the tube-dominance test and the resident intruder test. The researchers found out that, adolescent mice that experienced early life maternal separation were five times more dominant and had a higher number of attacks in the resident-intruder test. They concluded that early life stress due to maternal separation might induce anxiety- and aggressive-like behavior during adolescence and that this might be associated with synaptic plasticity of the hippocampus.[10]

Playful and affiliative behavior

Both human and rodent adolescents have been known to have elevated levels of social, playful and affiliative behavior when compared to adult.[3] These behaviors are important to establish adult-like social relationships or hierarchies.[1] In order to test these behaviors, a focal animal-all occurrences sampling method can be used to score different affiliative behaviors. These playful and affiliate behaviors include investigative elements, e.g. social sniff: partners are mutually sniffing each other’s anogenital region; affiliative elements, e.g. social rest: rat is being groomed by the partner; play soliciting, e.g. pushes its own snout or the whole anterior part of its body under the partner’s body; rough-and-tumble play, e.g. the two rats exhibit sudden darting movements, which are associated with pouncing on the partner back, chasing, wrestling and pinning.[11][12]


Adolescence is a developmental phase of which the borders are hard to define. Generally, it is characterized by behaviors that allow individuals to grow more independent from parental care, i.e., for example, increased playful and affiliative behaviors associated with partner seeking. Knowing that several behavioral disorders often show up during adolescence, it is an important phase to study. The periadolescent rat has been known to be a useful and translational model to study the different behaviors that mark human adolescence. These behaviors include higher tendency for novelty seeking, which goes hand in hand with risk-taking and exploratory behaviors. Taken together these behaviors could explain why adolescents have a higher probability to initiate drugs, while they are also more sensitive to its effects and to develop addictions. Furthermore, earlier life experiences could also influence behaviors that occur during adolescence, e.g. early life maternal separation could cause increased anxiety-like behaviors in adolescents.  Overall, more research is needed on the underlying mechanisms of these behaviors in order to fully understand adolescence as a whole.


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