When is a mouse adolescent

Trends Neurosci 26 : — Holmes A, Rodgers RJ Influence of spatial and temporal manipulations on the anxiolytic efficacy of chlordiazepoxide in mice previously exposed to the elevated plus-maze.

Neurosci Biobehav Rev 23 : — Stages of progression in drug involvement from adolescence to adulthood: further evidence for the gateway drug theory. J Study Alcohol 53 : — Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence.

Neurosci Biobehav Rev 27 : 19— Risk-taking during exploration of a plus-maze is greater in adolescent than in juvenile or adult mice. Anim Behav 64 : — Cellular and synaptic mechanisms of nicotine addiction.

J Neurobiol 53 : — Nicotine preconditioning antagonizes activity-dependent caspase proteolysis of a glutamate receptor. J Biol Chem : — Nestler EJ Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2 : — Common molecular and cellular substrates of addiction and memory. Neurobiol Learn Memory 78 : — Pharmacol Biochem Behav 49 : — Corticosterone levels determine individual vulnerability to amphetamine self-administration.

Acetylcholine receptors containing the beta 2 subunit are involved in the reinforcing properties of nicotine. Nature : — Chronic nicotine exposure reduces NMDA receptor-mediated damage in the hippocampus without altering calcium accumulation or extrusion: evidence of calbindin-D28K overexpression. Neuroscience : 75— Limbic-striatal memory systems and drug addiction.

Age of onset of drug use as a factor in drug and other disorders. Google Scholar. N -methyl- D -aspartate receptor antagonism in the ventral tegmental area diminishes the systemic nicotine-induced dopamine release in the nucleus accumbens. Neuroscience 82 : — Slotkin TA Nicotine and the adolescent brain: insights from an animal model.

Neurotoxicol Teratol 24 : — Spear LP The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24 : — Periadolescence: age-dependent behavior and psycho-pharmacological responsivity in rats.

Dev Psychobiol 16 : 83— Stamford JA Development and ageing of the rat nigrostriatal dopamine system studied with fast cyclic voltammetry. J Neurochem 52 : — Extinction-induced upregulation in AMPA receptots reduces cocaine-seeking behaviour. Nature : 70— Taioli E, Wynder EL The importance of age of starting smoking. N Engl J Med : — Evidence for dopamine receptor pruning between adolescence and adulthood in striatum but not nucleus accumbens.

Dev Brain Res 89 : — J Health 63 : — CAS Google Scholar. Adolescent nicotine exposure produces immediate and long-term changes in CNS noradrenergic and dopaminergic function.

Brain Res : — Adolescent nicotine exposure causes persistent upregulation of nicotinic cholinergic receptors in rat brain regions. Brain Res : 9— Novelty seeking, risk taking, and related constructs as predictors of adolescent substance use: an application of Cloninger's theory. J Subst Abuse 6 : 1— Synaptic plasticity in drug reward circuitry. Wise RA Addictive drugs and brain stimulation reward. Annu Rev Neurosci 19 : — A psychomotor stimulant theory of addiction.

Psychol Rev 94 : — Brain Res : 32— Download references. We wish to thank Angelina Valanzano for expert technical assistance. You can also search for this author in PubMed Google Scholar.

Correspondence to Giovanni Laviola. Reprints and Permissions. Adriani, W. Neuropsychopharmacol 29, — Download citation. Received : 11 July Revised : 28 October Accepted : 31 October Published : 03 November Issue Date : 01 May Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

Neurotoxicity Research Frontiers in Zoology Psychopharmacology Advanced search. Skip to main content Thank you for visiting nature. Download PDF. Introduction Adolescence is for all of us, a very important and defining period of our lives. 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 Behavioral Assessment of Rodent model of Adolescence There are various ways for testing the above mentioned behavioral traits of periadolescent rodents.

Novelty seeking Both rodent and human adolescents have been known to show high-risk behavior, which can result in the initiation of drugs. Drug sensitivity As mentioned before, compared to adults, adolescents have a higher probability of initiating and using soft as well as hard drugs.

Conclusion Adolescence is a developmental phase of which the borders are hard to define. Ann N Y Acad Sci. Urbonaite B, Hindmarsh P. Onset of breast and pubic hair development in preadolescent Lithuanian schoolgirls. Spear LP. Vol Risk taking during exploration of a plus-maze is greater in adolescent than in juvenile or adult mice. Long-term effects of chronic nicotine on emotional and cognitive behaviors and hippocampus cell morphology in mice: comparisons of adult and adolescent nicotine exposure.

Eur J Neurosci Behav Neurosci. Pharmacol Biochem Behav. Author Details. Maze Engineers. MazeEngineers makes behavioral mazes for all species with high precision and accuracy. Each maze is hand made for exacting specifications, with automation, AI integration and open software integration.

Contact us: Contact Mazeengineers. Please inquire about bulk order discounts. MazeEngineers products are NOT designed for human consumption, testing, or clinical utilization. However, it had no effects in other assays for avoidance behavior or on fear conditioning, alcohol drinking, reward or aversion sensitivity, or novel object exploration in either sex.

Adolescence is a critical developmental period marked by increased reward-seeking and impulsivity and the establishment of apposite social behaviors Spear, ; Steinberg, , ; Romer, ; Leshem, In humans, adolescence is associated with increased peer affiliation and separation from family Noom et al.

In rodents and other mammals, it is marked by the heightened incidence of play behavior, altered social interactions, and increased exploration Spear, ; Hawk et al. The quality and quantity of social interactions during adolescence have been linked to later-life behavioral outcomes in humans, including rates of drug and alcohol use and the formation of healthy social relationships Bray et al. Adolescence is also marked by increased stress sensitivity, and chronic stress exposure during this period has been shown to alter brain structure and function Paus, ; Eiland and Romeo, As peer interactions are especially important during adolescence Steinberg, ; Jager et al.

This increased stress sensitivity may partly explain why substance use disorders and many other psychiatric conditions frequently emerge during adolescence Turner and Lloyd, ; Kessler et al. Also, circulating gonadal hormones that emerge at puberty may influence stress responses in adolescence by modulating arousal and salience of stressful stimuli, and additionally can physiologically interact with stress hormones to alter behavior in a sex-specific manner during development and adulthood Romeo et al.

Understanding how adolescent social stress alters neurophysiology and behavior may prove crucial to treating stress-related disorders in adolescence and throughout later life. Adolescent social isolation in rats has emerged as a preclinical model that recapitulates many of the deleterious behavioral outcomes linked to chronic adolescent stress in humans Lukkes et al.

In male rats, this paradigm has been shown to increase anxiety-like behavior and drug and ethanol intake and decrease fear memory extinction McCool and Chappell, ; Whitaker et al. Isolation during adolescence has also been linked to decreased social interaction in rats Ferdman et al. Less is known about the effects of protracted adolescent isolation on these behaviors in mice, even though they are commonly used in neuroscience research, including studies that model human psychiatric conditions such as drug self-administration that require individual housing Becker and Ron, Like humans, adolescent mice demonstrate a potentiated response to stress Romeo et al.

Although there are some reports that chronic isolation beginning in adolescence increases depressive- and anxiety-like behaviors and drug self-administration in mice Lopez et al. However, the lasting behavioral effects of social isolation either in adolescence or adulthood on escalated alcohol self-administration and anxiety-like behaviors in this strain have been variable Lopez et al.

Following 6 weeks of social isolation beginning in either adolescence or adulthood, we measured anxiety, anhedonia, alcohol intake, reward and aversion sensitivity, fear memory formation, and social behavior in adulthood.

We found that social isolation produced few behavioral deficits overall, however, exposure to this manipulation beginning in adolescence led to aberrant social behavior in adulthood, marked by hyper-sociability and reduced avoidance behavior. One week after arrival, mice were randomly assigned to socially isolated SI, one mouse per cage or maintained in group-housed GH, five mice per cage conditions for 6 weeks before behavioral testing.

In the adolescent SI cohort, mice that were GH through adolescence were singly housed at PD77 for the duration of the study. In the adult SI cohort, GH mice remained in group-housed conditions.

Assays were conducted under lux lighting conditions as previously described Pleil et al. All behavioral experiments commenced 2 h into the start of the dark cycle.

Timeline graphs illustrating the sequence of experiments conducted in the adolescent and adult isolation cohorts can be found in Figures 1A , 2A , respectively. Figure 1. Adolescent social isolation behavior battery. A Experimental timeline. B In the elevated plus-maze EPM , adolescent social isolation SI increases the percent time spent exploring the open arms, an effect driven by females left , without altering locomotor activity as measured by closed arm entries right.

C Adolescent SI oppositely affects the percent time spent exploring the center of an open field in males and females left but does not affect the distance traveled in this assay right. D On the social interaction test, all but group-housed GH females display a significant preference for a novel social partner over an empty cup, and adolescent SI increases preference left without impacting total time spent exploring both objects right.

F All groups display a preference for a novel object over a familiar one, and this preference was greater in males than females but unaffected by adolescent SI left. The total time spent exploring both objects is likewise increased in males compared to females right. G Females display enhanced fear conditioning compared to males, but adolescent SI does not alter this measure. At the beginning of each trial, the mouse was placed in the center of the maze facing an open arm, and movement was tracked continuously for 5 min.

The total time spent on the open and closed arms of the assay and the total number of open and closed arm entries defined as placement of all four paws into the arm were quantified. Percent time spent in the open arms of the assay was calculated to measure anxiety-like behavior, and closed arm entries were used as a measure of locomotion.

The mouse was placed in one corner of the arena and allowed to explore freely for 30 min. The total distance traveled in the maze cm was used to measure locomotion, and percent time in the center of the maze was used to assess anxiety-like behavior.

The two compartments were separated by a divider with a 6 cm x 6 cm cut out passageway at floor level. At the beginning of each trial, the mouse was placed in a corner of the light compartment and allowed to move freely between the two compartments for 10 min.

The number of lightbox entries and total time spent in the light compartment as compared to the dark compartment was used to assess anxiety-like behavior. The placement of the cups and social partner were pseudorandom and counterbalanced.

Interaction zones for each cup were defined as encompassing a 5 cm radius around the center of the cup, and the ratio of interaction time with the social partner vs.

The novel object interaction assay was conducted under the same conditions and using the same analyses as the social interaction test see above but using objects, to assess whether effects observed in novel social partner preference could be generalized to a non-social novel object.

The objects were affixed to the floor of the arena during behavioral testing, which proceeded as follows: phase 1: empty arena; phase 2: two versions of the same object located at opposite corners of the arena 10 cm from each wall; phase 3: a novel object replaced one of the two familiar objects in the arena. The ratio of interaction time with the novel vs. Fear conditioning was performed in an operant box with a stainless-steel grid floor within a sound-attenuating chamber Colbourn Instruments, Allentown, PA, USA.

The mouse was placed in the chamber at the beginning of the test, and following a 5 min habituation period received six pairings of a 30 s, 80 dB tone conditioned stimulus, CS co-terminating with a 2 s, 0.

We used a modified version of the standard Drinking in the Dark DID binge ethanol drinking paradigm mDID to assess binge ethanol intake under limited-access conditions as well as h preference for ethanol over water.

Mice were singly housed for several days before the first ethanol presentation. On day 4, two bottles one containing ethanol solution, one containing water were placed in the cage for 24 h bottles were weighted after 2 h, 4 h, and 24 h of access. Bottle weights were used to calculate ethanol and water consumption daily normalized to body weight and 24 h ethanol preference on day 4, calculated as the ratio of the volume of liquid consumed from the ethanol bottle to the water bottle.

Consumption and preference of quinine-adulterated ethanol over water in a two-bottle choice home cage assay was measured to evaluate aversion-resistant ethanol drinking behavior. Bottle placement was pseudorandom and switched daily, and consumption and preference were measured as described for mDID. Intake and preference were measured every 24 h for four consecutive days. The novel mouse was placed into the cage and overhead video was used to record behavior for 5 min.

An experimenter blind to condition hand-scored discrete behaviors performed by the experimental mouse, including the number and duration of the total, head-to-head, and head-to-tail social interactions, as well as digging and climbing bouts.

Statistical analyses were conducted using GraphPad Prism 8 software. No animal was excluded from analysis on more than one behavioral assay. Significant effects in all ANOVAs were followed up with post hoc two-tailed t -tests corrected for multiple comparisons using the Holm-Sidak method, and adjusted p -values are presented. Alpha values of 0. In contrast, social isolation during adulthood did not alter anxiety-like behavior on the EPM Figure 2B.

Figure 2. Adult isolation behavior battery. B Females spend more time exploring the open arms of the EPM, but adult SI does not influence this measure left ; there is no difference in general locomotor behavior, measured by the number of entries into the closed arms right.

C There are no effects of sex or adult SI on the percent time spent exploring the center of the open field OF; left , however, there is a sex-dependent effect of adult SI on the total distance traveled in the OF right. D Adult SI does not alter preference for a novel social partner over an empty cup in the social interaction test left but does decrease total time spent interacting with the social partner and empty cup, an effect driven by males right.

GH males also spend more total time exploring both objects compared to GH females. F In the novel object interaction test, all groups except GH males display a preference for a novel vs. To determine whether the increased social exploration observed following adolescent social isolation could be generalized to non-social contexts, we performed a novel object interaction task designed similarly to the social interaction task described above Figure 1F.

To assess general exploratory behavior in this assay, we compared the total time that animals in each group spent exploring both the novel plus familiar objects in this assay. Altogether, these results suggest that while there are sex differences in the preference for and exploration of novel objects over familiar, adolescent social isolation had no effect on this task. In contrast, adolescent social isolation increased preference for a social partner, suggesting that its effects were specific to a social context.

As previous studies in rodents have demonstrated that adolescent social isolation increases home cage ethanol self-administration McCool and Chappell, ; Butler et al. We also found no effect of social isolation on ethanol preference at either concentration in females Figure 3A , right. Figure 3. Effects of adolescent social isolation on home-cage ethanol drinking and reward and aversion sensitivity in adult female A—C and male D—F mice. B Adolescent GH and SI females display similar consumption of quinine-adulterated ethanol left and preference for it over water right across multiple quinine concentrations.

Similar to females, social isolation did not affect ethanol consumption or preference in males Figure 3D , left. In male mice, no differences in sucrose preference emerged Figure 3F ; main effect of time: F 1. Altogether, results from our drinking experiments suggest that binge ethanol consumption, aversion-resistant ethanol intake, and general reward sensitivity were unaltered by adolescent social isolation. Gilpin, N.

The central amygdala as an integrative hub for anxiety and alcohol use disorders. Psychiatry 77, — Goldsmith, J. Effects of the duration of individual or group housing on behavioural and adrenocortical reactivity in male mice. Gonzales, R.

Alcohol and glutamate. Alcohol Health Res. World 21, — Gordon, J. Anxiolytic drug targets: beyond the usual suspects. Goulding, S. Accumbens Homer2-mediated signaling: a factor contributing to mouse strain differences in alcohol drinking? Genes Brain Behav. Gremel, C. Involvement of amygdala dopamine and nucleus accumbens NMDA receptors in ethanol-seeking behavior in mice. Neuropsychopharmacology 34, — Hilakivi, L. Hodge, C. Kalivas, P. Glutamate transmission in addiction. Neuropharmacology 56, — Neural systems for behavioral activation and reward.

Kelley, A. Risk taking and novelty seeking in adolescence: introduction to part I. Kliethermes, C. Anxiety-like behaviors following chronic ethanol exposure. Anxiety-like behavior in mice in two apparatuses during withdrawal from chronic ethanol vapor inhalation. Koltunowska, D. The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats.

Psychiatry 45, — Koob, G. Neuroadaptive mechanisms of addiction: studies on the extended amygdala. Kotlinska, J. The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats.

Lee, K. Binge alcohol drinking elicits persistent negative affect in mice. Lee, A. Protein kinases and addiction. Lesscher, H. Amygdala protein kinase C epsilon controls alcohol consumption. Liu, Z.

Inhibition of CaMKII activity in the nucleus accumbens shell blocks the reinstatement of morphine-seeking behavior in rats. Lum, E. Neuropharmacology 79, — MacPherson, L. Changes in sensation seeking and risk-taking propensity predict increases in alcohol use among early adolescents. Mao, L. Sheng Li Xue Bao 66, — Marshall, J.

Alcohol and substance abuse in panic disorder. Psychiatry 58, 46—50; discussion 49— Martin, C. Diagnosis and assessment of alcohol use disorders among adolescents. World 22, 95— Martinez, G. Misslin, R. Responses in mice to a novel object. Mogenson, G. From motivation to action: functional interface between the limbic system and the motor system.

Morishima, Y. Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice. U S A , — Myers, M. Coping responses and relapse among adolescent substance abusers. Abuse 2, — National Institute on Alcohol Abuse and Alcoholism. A call to action: changing the culture of drinking at U. NIAAA council approves definition of binge drinking.

CrossRef Full Text. Alcohol overdose: the dangers of drinking too much. NIH Factsheet Publication. Nauczyciel, C. The nucleus accumbens: a target for deep brain stimulation in resistant major depressive disorder.

Psychiatry Evaluation of marble-burying behavior as a model of anxiety. Novier, A. Alcohol use across the lifespan: an analysis of adolescent and aged rodents and humans. Effects of intoxicating free-choice alcohol consumption during adolescence on drinking and impulsivity during adulthood in selectively bred high-alcohol preferring mice.

Paxinos, G. The Mouse Brain in Stereotaxic Coordinates. Pierce, R. Psychostimulant-induced neuroadaptations in nucleus accumbens AMPA receptor transmission. Cold Spring Harb. Pohorecky, L. Stress and alcohol interaction: an update of human research. Porsolt, R. Behavioral despair in mice: a primary screening test for antidepressants.

Depression: a new animal model sensitive to antidepressant treatments. Nature , — Rodent models of depression: forced swimming and tail suspension behavioral despair tests in rats and mice. Chapter 8:Unit 8. Qi, J. Quintero, G. Role of nucleus accumbens glutamatergic plasticity in drug addiction. Rada, P.

Neuroscience , — Robbins, T. Behavioural and neurochemical effects of early social deprivation in the rat. Salamone, J. The involvement of nucleus accumbens dopamine in appetitive and aversive motivation. Salgado, S. The nucleus accumbens: a comprehensive review. Scheyer, A. AMPA receptor plasticity in accumbens core contributes to incubation of methamphetamine craving. Psychiatry 80, — Seif, T.