Search

The fulfillment of belonging needs underlies a variety of behaviors. In order to understand how social needs unmet during maturation shape everyday life, we examined social motivation and cognition in peripubertal rats, as a rodent model of adolescence, subjected to social isolation (SI) during early and early-to-mid adolescence. The behavioral correlates of social orientation (social space preference), sociability (preference for social over non-social novelty), and social novelty preference (SNP) were examined in group-housed (GH) and single-housed (SH) rats in a 3-chamber test. The response to social odors was examined to gain insights into the developmental role of social odors in motivated social behavior. Differentiation between appetitive (number of visits/approaches) and consummatory (exploratory time) aspects of motivated social behavior was done to determine which facet of social motivation characterizes maturation when social needs are met and which aspect dominates when social needs are unsatisfied. The SI-sensitive parvalbumin-expressing interneurons (PVI) in the hippocampus were examined using immunohistochemistry. The main findings are the following: (1) in GH rats, the preference for social space is not evident regardless of animals’ age, while sociability becomes apparent in mid-adolescence strictly through consummatory behavior, along with complete SNP (appetitive, consummatory); (2) SH promotes staying in a social chamber/space regardless of animals’ age and produces an appetitive preference for it only in early-adolescent animals; (3) SH promotes sociability (appetitive, consummatory) regardless of the animals’ age and prevents the SNP; (4) the preference for a social odor is displayed in all the groups through consummatory behavior, while appetitive behavior is evident only in SH rats; (5) the response to social odors does not commensurate directly to the response to conspecifics; (6) SH does not influence PVI in the hippocampus, except in the case of early-adolescence when a transient decrease in the dentate gyrus is observed. These results accentuate the developmental complexity of social motivation and cognition, and the power of SI in adolescence to infringe social maturation at different functional levels, promoting appetitive behavior toward peers overall but harming the interest for social novelty. The findings emphasize the importance of the fulfillment of basic social needs in the navigation through the social world.

Background: Psychotic states related to psychostimulant misuse in patients with hepatitis C virus infection may complicate acceptance and reaction to antiviral treatment. This observation equally applies to the widely used ribavirin therapy. Objective: We examined psychomotor and body weight gain responses to low ribavirin doses after cessation of intermittent amphetamine treatment in adult rats to assess its role in neurobehavioral outcome during psychostimulant withdrawal. Method: The model of amphetamine-induced (1.5 mg/kg/day, i.p., 7 consecutive days) motor sensitization and affected body weight gain was established in adult male Wistar rats. Then, additional cohort of amphetaminesensitized rats was subjected to saline (0.9% NaCl; 1 mL/kg/day; i.p.) or ribavirin (10, 20 and 30 mg/kg/day, i.p.) treatment for 7 consecutive days. Animals’ motor activity in a novel environment was monitored after the 1st and the 7th saline/ribavirin injection. Body weight gain was calculated as appropriate. Determination and quantification of ribavirin in the brain tissue were performed also. Results: The 1st application of ribavirin to amphetamine-sensitized rats affected/decreased their novelty-induced motor activity only at a dose of 30 mg/kg. After the 7th application, ribavirin 30 mg/kg/day still decreased, while 10 and 20 mg/kg/day increased novelty-induced motor activity. These behavioral effects coincided with the time required to reach maximum ribavirin concentration in the brain. Body weight gain during withdrawal was not influenced by any of the doses tested. Conclusion: Ribavirin displays central effects that in repeated treatment, depending on the applied dose, could significantly influence psychomotor response but not body weight gain during psychostimulant/amphetamine withdrawal.

Propofol is a versatile, short-acting, intravenous sedative-hypnotic agent that rapidly crosses the blood-brain barrier resulting in rapid action, short duration of action, and minimal side effects. It is also widely used for the sedation of patients in the intensive care unit and in those undergoing brief ambulatory surgery. Considering wide usage of propofol in all age groups of patients, this chapter summarizes mechanisms underlying its therapeutic action, changes at molecular level suspected to trigger the unwanted functional impairments related to its application during critical periods of mammalian development, and the role of ventral tegmental area dopamine neurons in the emergence from propofol anesthesia, overall emphasizing context-dependent influence of propofol anesthesia on neural networks and brain functions.

Reduction in direct social contact with peers during early adolescence is thought to be a risk factor for an increase in depressive symptoms, but there is still no clear evidence to suggest early behavioral manifestations and their association with the later outcome of social distancing during this period. To address this question, we used social isolation paradigm in peripubertal rats as the rodent model of adolescence. The litter was an experimental unit. On postnatal day 29, each litter gave group-housed and single-housed males, which were reared and tested one week and two weeks thereafter. Psychomotor/emotional response to novelty in exploration-based tasks, behavioral and neuronal responses to the drug reward (D-amphetamine), motivation/hedonic behavior, physiological and response to physiological stress were examined. Social isolation in peripubertal rats manifested through: hyper-reactivity/agitation and the state anxiety/risk-taking at an early stage; reduced behavioral response to D-amphetamine and altered neural processing of this stimulus, at a later stage; consummatory hypohedonia that deepened over time without changing the motivation to eat; unchanged body weight gain and resting blood corticosterone, cortisol and glucose levels over time; altered blood biochemistry (silenced corticosterone and increased glucose) due to overnight fasting only at an early stage. Our results highlight that the outcome of reduced direct social contact with peers during peripuberty is dynamic, with the cluster of atypical early symptoms that evolve into the syndrome that is delicate for assessment through routinely measurable behavior and biomarkers of stress, but with progressive consummatory hypohedonia and unaffected motivation to eat as stable marks.

Background The effects of anesthetic drugs on postoperative cognitive function in children are not well defined and have not been experimentally addressed. Aims The present study aimed to examine the influence of propofol anesthesia exposure on nonaversive hippocampus-dependent learning and biochemical changes involved in memory process in the dorsal hippocampus, in peripubertal rats as the rodent model of periadolescence. Methods The intersession spatial habituation and the novel object recognition tasks were used to assess spatial and nonspatial, nonaversive hippocampus-dependent learning. The exposure to anesthesia was performed after comparably long acquisition phases in both tasks. Behavioral testing lasted for 2 consecutive days (24-hour retention period). Changes in the expression of molecules involved in memory retrieval/reconsolidation were examined in the dorsal hippocampus by Western blot and immunohistochemistry, at the time of behavioral testing. Results Exposure to propofol anesthesia resulted in inappropriate assessment of spatial novelty at the beginning of the test session and affected continuation of acquisition in the spatial habituation test. The treatment did not affect recognition of the novel object at the beginning of the test session but it attenuated overall preference to novelty, reflecting retrieval of a weak memory. The expression of phosphorylated extracellular signal-regulated kinase 2 (involved in memory retrieval) was decreased while the level of phosphorylated Ca2+ /calmodulin-dependent protein kinase IIα and early growth response protein 1 (involved in memory reconsolidation) was increased in the dorsal hippocampus. The level of Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog B (neuronal activity indicator) was increased in the dorsal dentate gyrus. Enhanced exploratory activity was still evident in the propofol anesthesia exposure (PAE) group 48 hour after the treatment in both tasks. Conclusion In peripubertal rats, propofol anesthesia exposure affects memory retrieval and acquisition of new learning in the spatial and nonspatial, nonaversive learning tasks 24 hour after the treatment, along with the expression of molecules that participate in memory retrieval/reconsolidation in the dorsal hippocampus. These results may have clinical implications, favoring control of basic cognitive functions in older children after the propofol exposure.

Adolescent neurodevelopment confer vulnerability to the actions of treatments that produce adaptations in neurocircuitry underlying motivation, impulsivity and reward. Considering wide usage of a sedative-hypnotic agent propofol in clinical practice, we examined whether propofol is a challenging treatment for peripubertal brain. Motivation/hedonic behavior (sucrose preference test), approach/avoidance behavior (elevated plus maze test) and response to dissociative drug phencyclidine (PCP) were studied in peripubertal rats (the rodent model of periadolescence) after propofol anesthesia exposure (PAE). Neurodegeneration (Fluoro-Jade staining) and the expression of proteins (Western blot) involved in excitatory synaptic transmission and activity-dependent synaptic stabilization in the medial prefrontal cortex (mPFC) and striatum (components of motivation/reward circuitry; process both appetitive and aversive events) were examined as well. In peripubertal rats PAE produced 1) transient brain-region specific changes in the expression of N-methyl-d-aspartate (NMDA) receptor subunits NR2A and NR2B, PSD-95 and N-cadherin, without neurotoxicity, 2) hyperlocomotor response to PCP, 3) no changes in preference for palatable 1% sucrose solution and a decrease in food eaten, 4) preference for 20% sucrose solution without changes in food eaten, 5) stretch-attended postures and open arms entries in the elevated plus maze test. Overall, these novel findings show that PAE leaves transient synaptic trace recognized as early form of synaptic plasticity related to passive drug exposure in the brain systems implicated in motivation/reward, increases drug-responsiveness, favors risk-taking and preference of novel/intense stimuli repairing otherwise present motivational deficiency. These findings accentuate multifaceted response to propofol in peripuberty and the importance of environmental stability for the most favorable neurobehavioral recovery.

Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400 mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities.