Learning In Adolescent Rats Research Articles

Behavioral changes and dendritic remodeling of hippocampal neurons in adolescent alcohol-treated rats.

Objective: Earlier, we and others have reported that alcohol exposure in adolescent rat impaired performance of a spatial memory task in the Morris water maze. The goal of the present study was to investigate the effects of acute adolescent alcohol treatment on the hippocampus-dependent (contextual fear conditioning) and hippocampus-independent (cued fear) memories. The study also looked at the structural changes in anterior CA1 hippocampal neurons in adolescent alcohol-treated rats. Methods: Adolescent female rats were administered with a single dose of alcohol (1.0, 1.5, or 2.0g/kg) or vehicle either before training (pre-training) or after training (pre-testing). Experimental and control rats were trained in the fear conditioning paradigm, and 24h later tested for both contextual fear conditioning as well as cued fear memory. Separate groups of rats were treated with either alcohol (2g/kg) or vehicle and sacrificed 24h later. Their brains were harvested and processed for rapid Golgi staining. Randomly selected CA1 pyramidal neurons were analyzed for dendritic branching and dendritic spine density. Results: Pre-training alcohol dose-dependently attenuated acquisition of hippocampus-dependent contextual fear conditioning but had no effect on the acquisition of amygdala-associated cued fear. When administered following training (pre-testing), alcohol did not alter either contextual conditioning or cued fear memory. Golgi stained CA1 pyramidal neurons in alcohol treated female rats had reduced basilar tree branching and less complex dendritic arborization. Conclusion: Alcohol specifically impaired hippocampal learning in adolescent rats but not amygdala-associated cued fear memory. Compared to vehicle-treated rats, CA1 hippocampal pyramidal neurons in alcohol-treated rats had less complex dendritic morphology. Together, these data suggest that adolescent alcohol exposure produces changes in the neuronal organization of the hippocampus, and these changes may be related to impairments in hippocampus-dependent memory formation.

Infralimbic EphB2 Modulates Fear Extinction in Adolescent Rats.

Adolescent rats are prone to impaired fear extinction, suggesting that mechanistic differences in extinction could exist in adolescent and adult rats. Since the infralimbic cortex (IL) is critical for fear extinction, we used PCR array technology to identify gene expression changes in IL induced by fear extinction in adolescent rats. Interestingly, the ephrin type B receptor 2 (EphB2), a tyrosine kinase receptor associated with synaptic development, was downregulated in IL after fear extinction. Consistent with the PCR array results, EphB2 levels of mRNA and protein were reduced in IL after fear extinction compared with fear conditioning, suggesting that EphB2 signaling in IL regulates fear extinction memory in adolescents. Finally, reducing EphB2 synthesis in IL with shRNA accelerated fear extinction learning in adolescent rats, but not in adult rats. These findings identify EphB2 in IL as a key regulator of fear extinction during adolescence, perhaps due to the increase in synaptic remodeling occurring during this developmental phase.

Long-term changes in adaptive behavior of rats after inflammatory pain stimulation during neonatal development

This study is devoted to the investigation of the functional activity of the tonic nociceptive system using the formalin test. We also studied the anxiety level indices, proneness to depression-like behavior and spatial learning in adolescent male rats exposed in the neonatal development to repeated pain stimulation induced by peripheral inflammation. The following groups of 25-day-old rats were used being exposed at the age of 7 and 8 days to: (1) pain stimulation by formalin injection with maternal deprivation for 1 h (FD), (2) same formalin-induced pain stimulation without maternal deprivation (FWD), (3) physiological saline injection with maternal deprivation for 1 h (PD), (4) physiological saline injection without maternal deprivation (PWD) and (5) no stimulation (intact rats). Our findings indicate that pain induced in 7–8-day-old rat pups by formalin injection into the hind leg plantar pad manifests itself at adolescence (25 days) in an inflammatory pain response enhancement under the same pain stimulation as in the formalin test, adaptive behavior disorder in the forced swim test, and spatial learning disability. Also of particular importance is our observation that short-term repeated maternal deprivation of the 7–8-day-old rat pups in the absence of inflammatory pain increases the depression-like behavior proneness index. Thus, the repeated inflammatory pain stimulation during the neonatal development brings about significant changes in the studied types of adaptive behavior as well as in spatial learning in adolescent rats.

Treatment with MDMA from P11–20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats

Previous studies in rats showed that postnatal day (P)11-20 exposure to +/-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) causes learning and memory deficits in adulthood. The emergence and permanence of these learning deficits are currently unknown. This study was designed to investigate learning and memory deficits in adolescent (P30 or P40) and older (P180 or P360) rats exposed to MDMA from P11-20. Within each litter half the animals were exposed to MDMA (20 mg/kg) and half to saline (SAL) twice a day (8 h apart) from P11-20. In experiment (exp) 1, behavioral testing began on either P30 or P40, whereas in exp 2, testing began on either P180 or P360. Offspring were tested in the Cincinnati water maze (CWM), a test of path integration learning (2 trials/day for 5 days), and the Morris water maze (MWM) (three phases, with 5 days of 4 trials/day and a probe trial on the sixth day per phase). MDMA-treated rats took longer to find the platform and traveled a greater distance to find the platform at all ages tested in all phases of the MWM. MDMA-treated animals also spent less time in the target quadrant during probe trials. In the CWM, P30 and P40 animals took longer to find the goal and committed more errors in locating the goal, while P180 and P360 MDMA-treated animals performed similarly to SAL-treated animals. The data suggest that the spatial learning and memory deficits induced by MDMA are long lasting, while the path integration deficits recover over time.

Ethanol impairs memory of a simple discrimination in adolescent rats at doses that leave adult memory unaffected

Adolescent rats are less sensitive than adults to the hypothermic, anxiolytic, motor impairing, hypnotic, and lethal effects of ethanol. In vitro experiments nevertheless suggest that hippocampal neural activity is more affected by ethanol in preweanling or adolescent rats than in adults. These data are complemented by in vivo results showing that pretraining ethanol impairs learning in adolescent rats at doses that do not affect adult learning. In order to determine if posttraining ethanol affects memory differently in adolescents than in adults, Sprague–Dawley albino rats of both ages were trained in an appetitively motivated odor discrimination in which they were required to dig in scented sand for sweetened cereal reward. Immediately after training subjects received intraperitoneal injections of 0, 0.5, or 1 g/kg ethanol (12.6%). At test, 48 h later, subjects were presented with unbaited discriminanda and the time (s) spent digging in the S+ and S− was measured. Adolescents, but not adults, showed impaired discrimination performance if training was followed by ethanol. A subsequent experiment discounted the possibility that impaired adolescent performance was due to ethanol-induced conditioned taste or odor aversions. It thus appears that relative to adults, memory in adolescent rats is more strongly affected by ethanol in a test of appetitive conditioning that excludes ethanol’s effects on sensory and motivational influences during the learning experience.