Effects of prenatal exposure to cocaine on conditional discrimination learning in adult rats.

Adult male rats that were gestationally exposed to cocaine and control offspring were trained on an instrumental conditioning task for assessment of the acquisition and reversal of an appetitive conditional discrimination based on olfactory cues. Offspring were derived from Sprague-Dawley dams that had received subcutaneous/ly (sc) injections of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on Gestational Days 8–20, pair-fed (PF) dams that were injected with saline, nutritional control dams (NC) that received saline injections, and nontreated control dams (LC). There were no differences among the prenatal treatment groups in acquisition of the barpress response or response rate throughout all phases of training. All prenatal treatment groups required approximately the same number of sessions to criterion on the initial odor discrimination. In contrast, adult C40 offspring required more sessions to acquire the reversal of the conditional discrimination than did animals from the other treatment groups (PF, NC, and LC). In addition, even at criterion performance for acquisition of the reversal discrimination, C40 animals exhibited lower accuracy on the 1st 10 responses and made significantly more errors before the 1st reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal exposure to cocaine on Morris water maze performance in adult rats.

The spatial memory of adult rats prenatally exposed to cocaine and that of control offspring was assessed using the Morris water maze. Offspring were derived from Sprague Dawley dams that received subcutaneous injection of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on gestational Days 8-20, pair-fed dams injected with saline, or nontreated control dams. After acquisition, the platform was moved to a new location (reversal phase). Probe trials were conducted at the end of acquisition and reversal training. On the 1st acquisition day, adult male and female offspring prenatally exposed to cocaine required significantly more time and traversed a greater distance to find the hidden platform than did control offspring. Despite these initial differences observed in C40 offspring performance, all of the rats were performing at equivalent levels at the time probe trials were conducted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human energy and work in a European village

In a mouse model of transplacental cocaine exposure we have demonstrated alterations in brain structure and function of offspring including disturbances of brain growth, disruption of neocortical cytoarchitecture, and transient as well as persistent behavioral deficits. One mechanism by which cocaine may alter fetal brain development is through cocaine-induced alpha-adrenergic-mediated (uterine) arterial vasoconstriction. In this study pregnant Swiss Webster (SW) mice were injected with cocaine HCl (20 or 40 mg/kg, SC) without any changes evident in mean arterial blood pressure (MAP) measurements. These physiology results suggest that in our mouse model, cocaine's transplacental effects on the fetus are not due to cocaine-induced maternal vasoconstriction, nor concomitant hypoperfusion of the fetus. In a separate series of experiments, pregnant SW dams were administered cocaine HCl at 40 mg/kg/day (COC 40), 20 mg/kg/day (COC 20), or 10 mg/kg/day (COC 10) [SC, divided in two daily doses, from embryonic day (E) 8 to E17 inclusive]. Additional groups of cocaine-treated dams were administered phentolamine (5 mg/kg, SC), a short-acting alpha-adrenergic antagonist, 15 min prior to each cocaine dose (Phent COC 40, Phent COC 20, Phent COC 10). Animals born to Phent COC 40 dams demonstrated transient postnatal brain growth retardation and behavioral deficits in first-order conditioning of P9 mice comparable to mice born to COC 40 dams, which received the same regimen of cocaine injections without phentolamine pretreatment. Like COC 40 offspring, Phent COC 40 offspring also demonstrated a persistent deficit in the blocking paradigm. The behavioral and growth findings confirm and extend the physiology data, and imply that in our rodent model, alpha-adrenergic mechanisms (including maternal vasoconstriction) are unlikely to mediate these toxic effects of transplacental cocaine exposure on developing brain.     

Encoding specific associative memory: Evidence from behavioral and neural manipulations.

Within-subjects procedures with rats assessed the associative structures acquired during conditioning trials in which the interval between the stimuli and food was either short or long (i.e., A–10 s→food and B–40 s→food). In Experiments 1 and 2, after these conditioning trials, A and B served as second-order reinforcers for 2 further stimuli (i.e., X→A and Y→B); whereas Experiment 3 used a sensory preconditioning procedure in which X→A and Y→B trials occurred before the conditioning trials, and rats were finally tested with X and Y. In each experiment, Y elicited greater responding at test than did X. This finding supports the contention that the long-lived trace of B (associated with food on B–40 s→food trials) is more similar to the memory of B that was associatively provoked by Y, than is the short-lived trace of A (associated with food on A–10 s→food trials) to the memory of A that was associatively provoked by X. These conclusions were reinforced by the effects of a neural manipulation that disrupted discrimination learning involving the short traces of stimuli but not the long traces of the same stimuli. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Alterations in the reinforcing efficacy of cocaine in adult rats following prenatal exposure to cocaine.

Adult male rats gestationally exposed to cocaine and nonexposed control offspring were examined for differences in operant responding for cocaine and sucrose reinforcement. Offspring were derived from dams that had received subcutaneous injections of 40 mg/kg/3cc cocaine hydrochloride daily on gestational Days 8–20 and nontreated control dams. Although no prenatal treatment differences were seen when the animals lever pressed for sucrose pellets on a progressive-ratio (PR) schedule, adult offspring prenatally exposed to cocaine were observed to exhibit an enhanced rate of cocaine intravenous self-administration on a fixed-ratio 5 (FR-5) schedule along with a marked decrease in break point on the PR reinforcement schedule. These results suggest that the reinforcing efficacy of cocaine may be reduced in animals with a prenatal history of cocaine exposure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactive effects of prenatal cocaine and nicotine exposure on maternal toxicity, postnatal development and behavior in the rat

Two experiments were performed to investigate the interactive effects of prenatal coadministration of cocaine hydrochloride (C) and nicotine tartrate (N). Experiment I was designed to determine doses of C and N that could be coadministered without altering maternal gestational parameters and/or fetal viability. Exposure of Sprague-Dawley rats to combined high-dose C (20 mg/kg) and high-dose N (5.0 mg/kg) on gestation days 8-21 was not more toxic to dam or fetus that that of exposure to C alone. Experiment II investigated pregnancy outcome, postnatal development, and behavior of the offspring following drug exposure to either high-dose cocaine (20 mg/kg: CS), high-dose nicotine (5.0 mg/kg: NS), or both (NC) on gestation days 8-21. N was administered by osmotic minipump and C by sc injection. Saline-injected dams, fitted with saline-fitted pumps (SS), and untreated dams, pair-fed (PF) to NC females, served as controls. Alterations in maternal variables were limited to a 10-15% decrease in food consumption in NC and CS groups. Pregnancy outcome and birth statistics were unaffected by prenatal treatment, as was offspring body weight during the first four postnatal weeks. However, the development of surface righting was delayed inC CS pups, and only CS offspring were underresponsive to the stimulatory effects of dopamine agonists on activity and stereotypy. Behavioral responses to N challenge were similar in all groups. In addition, only CS offspring showed altered behavioral responses in a spontaneous alternation task. Treatment effects on dopamine D1 and D2 binding in the caudate nucleus were not observed. The combination of N and C did not exacerbate any of the behavioral changes seen in CS offspring. These results support the hypothesis that C is a behavioral teratogen in rodents, and suggest that in the present model, nicotine can mitigate some of the consequences of in utero exposure to cocaine.     

Noradrenaline and sensory preconditioning in the rat.

Two experiments investigated the effect of noradrenaline (NA) depletion following intraperitoneal administration of the neurotoxin N-2-chloroethyl-N-ethyl-2-bromobenzylamine ({dsp4}[50 mg/kg]) on sensory preconditioning in male Sprague-Dawley rats. For sensory preconditioning, a saccharin taste conditioned stimulus (CS?) and a special type of drinking bottle (noisy bottle) were paired during Phase 1. During Phase 2, the noisy bottle (CS?) was paired with lithium chloride, and during Phase 3 the aversion to saccharin (CS?) was tested in saccharin preference tests. {dsp4} treatment disrupted Ss' ability to form sensory preconditioning, and this effect could not be explained on the basis of enhanced neophobia, stimulus generalization, or a deficit in 1st-order conditioning in {dsp4}-treated Ss. Findings are discussed in relation to issues of associative learning such as contextual control of latent inhibition and extinction. Data suggest that NA-depleted rats fail to form associations between the CS? and CS? during sensory preconditioning and are consisitent with other data from compound conditioning experiments on the functional role of NA in learning and memory. (53 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation of phototactic suppression in Hermissenda by a chemosensory stimulus during compound conditioning.

Modifications of Hermissenda's phototactic behavior by compound pairings of light, scallop extract, and rotation were assessed. In general, the scallop extract potentiated phototactic suppression. Potentiation was dependent on (a) conjunctive presentations of scallop and light, (b) number of conditioning trials, and (c) scallop extract concentration. In related experiments, no second-order conditioning or sensory preconditioning of phototactic suppression was observed, indicating that within-compound associations did not contribute appreciably to potentiation. These results represent the first detailed analysis of compound conditioning in a mollusk using discrete presentations of well-characterized conditioned stimuli from distinct sensory modalities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal cocaine alters social competition of infant, adolescent, and adult rats

This series of experiments examined whether gestational cocaine exposure alters later social behavior exhibited during competition for biologically relevant stimuli. Rat offspring were derived from dams that received subcutaneous injections of 40 mg/kg/3cc cocaine HCl daily on gestational Days 8-20, pair-fed dams injected with saline, or nontreated control dams. Offspring competed with peers for access to a nipple in infancy, and to water in adolescence or adulthood. Prenatal cocaine exposure resulted in a decreased ability of cocaine-exposed infant rats to compete successfully for a nipple. Although adolescent and adult cocaine-exposed rats were no less successful than controls when competing for water, they exhibited a notable increase in aggression toward competitors during testing. Data provide evidence of alterations in social behavior and social competition as a result of prenatal cocaine exposure.     

Impaired trace fear conditioning following neonatal ethanol: Reversal by choline.

Neonatal ethanol exposure in animals results in performance deficits on tests of hippocampus-dependent spatial memory, and recent studies have shown that extra dietary choline can ameliorate some of these impairments. In this experiment, rats were administered 5.25 g/kg ig ethanol per day or sham intubations on Postnatal Days (PD) 4-9 and choline (0.1 ml of an 18.8 mg/ml solution) or saline subcutaneously on PD 4-20. On PD 30, rats were given delay or trace fear conditioning trials and were tested for conditioned stimulus-elicited freezing 24 hr later. Neonatal ethanol produced a profound impairment in trace conditioning that was reversed by choline. Groups did not differ in delay conditioned responding, indicating that neonatal ethanol produces a relatively selective cognitive deficit that can be alleviated with supplemental choline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Observational conditioning of snake fear in rhesus monkeys.

Hypothesized that observational conditioning is involved in the origins of many human and nonhuman primates' fears and phobias. In Exp I, a new index of snake fear in 7 19–28 yr old wild-reared rhesus monkeys and 9 laboratory-reared offspring (aged 8 mo to 6 yrs) was tested. Results show the measure was useful and demonstrated that young Ss raised by parents who had a fear of snakes did not acquire the fear in the absence of any specific experience with snakes. In Exp II, using 5 of the wild-reared Ss and 6 of the laboratory-reared Ss from Exp I, 5 of 6 offspring acquired an intense and persistent fear of snakes as a result of observing their wild-reared parents behave fearfully in the presence of real, toy, or model snakes for a short period of time. The fear was not context specific and showed no significant signs of diminution at 3-mo follow-up. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Possible anatomical basis of recovery of function after neonatal frontal lesions in rats.

Rats given medial frontal lesions on Postnatal Day 1 or Day 10 were trained on the Morris water task on Days 19–21 or Days 56–58. The operated groups were equally impaired at the water task on Days 19–21, but the Day 10 rats had recovered by 56 days. Dendritic arborization and spine density were analyzed in parietal layer II–III pyramidal cells. At Day 60, but not at Day 22, the Day 10 animals had more dendritic spines per unit dendritic length than did the controls or Day 1 rats. Thus, there was functional recovery rather than sparing after frontal lesions at 10 days, and the recovery was correlated with an increase in dendritic spines. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exogenous interferon delays luteal regression in red deer hinds (Cervus elaphus) by suppressing steroid-induced endometrial oxytocin sensitivity

Three groups of intact hinds (n = 10-18) and one group of ovariectomized hinds were treated with progesterone by mean, of Controlled Internal Drug Releasing (CIDR) devices for 13 days (device removal = Day 0). Group 1 served as controls; group 2 received injections of 4 mg recombinant bovine interferon-alpha,1 twice daily from Days 13 to 21; group 3 was run with a stag from Days 0 to 3, and all hinds were subsequently diagnosed pregnant; group 4 (ovariectomized) was treated with CIDR devices and estradiol to mimic steroid secretion during the estrous cycle. Progesterone profiles were determined from thrice-weekly plasma samples from Days -13 to 28. Rectal temperature was measured in a subset of groups 1 and 2 from Days 9 to 21. Oxytocin-induced prostaglandin F2 alpha release was measured in a subset of groups 1, 2, and 4 on Days 2, 4, 10, 16, and 18. Data are presented as means +/- SEM. Exogenous interferon delayed luteolysis (> or = 28 vs. 21.2 +/- 0.55 days, P < 0.0005) and induced transient pyrexia after the first injection (39.89 +/- 0.11 vs. 38.88 +/- 0.19 degrees C, p < 0.0005). Incidence of oxytocin-induced PGF2 alpha release in control hinds was greater on Days 2 and 18 than on Days 4 and 10 (8/8 and 7/8 vs. 3/8 and 0/8, respectively; p < 0.05) and was greater in control than in interferon-treated hinds on Days 16 and 18 (5/8 and 7/8 vs. 1/8 and 1/8, respectively; p < 0.05). Profiles of plasma progesterone concentration and oxytocin sensitivity in steroid-treated ovariectomized hinds did not differ from those in control hinds. These results suggest that steroid-controlled uterine oxytocin sensitivity is important in luteolysis and is suppressed by the administration of interferon, the putative embryonic pregnancy recognition signal in red deer.     

Ontogeny of dam–young recognition in captive Belding's ground squirrels (Spermophilus beldingi).

Investigated in 3 experiments the development of dam–young discrimination in Belding's ground squirrels by observing 8 dams retrieve unweaned young and by observing social interactions between dams and weaned young. Pups were cross-fostered at birth in order to examine how genetic relatedness (related or unrelated) and rearing association (familiar or unfamiliar) influenced discrimination. On Days 1 (24 hrs after fostering), 8, and 15 (Exp I), dams retrieved pups indiscriminately, but on Day 22 (about the time of weaning) dams retrieved familiar young (those they had reared) faster than unfamiliar young. On Day 29 (Exp II), familiar dam–young pairs were less agonistic during paired-encounter tests than were unfamiliar pairs. Results suggest that (a) dam–young discrimination is based on rearing association rather than genetic relatedness per se, and (b) discrimination emerges around weaning when dams and alien young first encounter each other under field conditions. In Exp III, olfactory cues seemed crucial to discrimination as determined by an olfactory impairment using zinc sulfate. (61 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of DNA glycosylases on spontaneous mutation

In the present study we examined the effects of phasic activation of the nucleus locus coeruleus (LC) on transmission of somatosensory information to the rat cerebral cortex. The rationale for this investigation was based on earlier findings that local microiontophoretic application of the putative LC transmitter, norepinephrine (NE), had facilitating actions on cortical neuronal responses to excitatory and inhibitory synaptic stimuli and more recent microdialysis experiments that have demonstrated increases in cortical levels of NE following phasic or tonic activation of LC. Glass micropipets were used to record the extracellular activity of single neurons in the somatosensory cortex of halothane-anesthetized rats. Somatosensory afferent pathways were activated by threshold level mechanical stimulation of the glabrous skin on the contralateral forepaw. Poststimulus time histograms were used to quantitate cortical neuronal responses before and at various time intervals after preconditioning burst activation of the ipsilateral LC. Excitatory and postexcitatory inhibitory responses to forepaw stimulation were enhanced when preceded by phasic activation of LC at conditioning intervals of 200-500 ms. These effects were anatomically specific in that they were only observed upon stimulation of brainstem sites close to (>150 micron) or within LC and were pharmacologically specific in that they were not consistently observed in animals where the LC-NE system had been disrupted by 6-OHDA pretreatment. Overall, these data suggest that following phasic activation of the LC efferent system, the efficacy of signal transmission through sensory networks in mammalian brain is enhanced.     

Ontogeny of preference for nutritive over nonnutritive suckling in albino rats.

Investigated nutritive vs nonnutritive suckling in 48 10–21 day old Sprague-Dawley rat pups in a spatial discrimination task. Ss preferred nutritive to nonnutritive suckling on their anesthetized mother at l7 and 21 days of age, but no preference was apparent in 10- and 12-day-old Ss. Rearing in isolation from the mother during Days 11–26 did not impair the development of preference for nutritive suckling in 16 17-day-old Ss. Thus, the appetitive component of suckling of infant rats, like the consummatory component, appears to come under the direct control of nutritional factors at the start of the weaning period. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous Recovery From Forward and Backward Blocking.

This article demonstrates and analyzes spontaneous recovery of stimulus control following both forward and backward blocking in a conditioned suppression preparation with rats. Experiment 1 found, in first-order conditioning, robust forward blocking and an attenuation of it following a retention interval. Experiment 2 showed, in sensory preconditioning, recovery of responding following both forward and backward blocking. Also, the results of this experiment indicated that response recovery to the blocked stimulus cannot be explained by an impaired status of the blocking stimulus after a retention interval. Experiment 3, also in sensory preconditioning, suggested that spontaneous recovery following both forward and backward blocking in Experiment 2 was due to impaired associative activation of the blocking stimulus' representation during testing with the blocked stimulus. Although no contemporary model of associative learning can explain these results, a modification of R. R. Miller and L. D. Matzel's (1988) comparator hypothesis is proposed to do so. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Overshadowing and the outcome-alone exposure effect counteract each other.

Three conditioned lever-press suppression experiments with rats investigated the interaction between overshadowing and outcome-alone exposure effects. Experiment 1 found in first-order conditioning that combined overshadowing and outcome-preexposure treatments attenuate the response deficit produced by either treatment alone. Experiments 2 and 3 investigated the interaction between overshadowing and outcome pre- and postexposure effects in sensory preconditioning, varying retention intervals to engage recency and primacy effects with respect to treatment order. Contrary to when a solitary cue is conditioned, responding to a cue conditioned in compound appeared positively correlated with the context's associative status. These findings suggested that some of the basic laws of learning applicable to cues conditioned alone do not similarly apply to a component of a compound cue. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High maternal intake of polyunsaturated fatty acids during pregnancy in mice alters offsprings' aggressive behavior, immobility in the swim test, locomotor activity and brain protein kinase C activity

Populations in Western countries consume an excess of polyunsaturated fatty acids (PUFA), even during pregnancy. Since (n-6) PUFA is critical for brain development, we studied whether a high maternal consumption of this fatty acid alters offsprings' affective-like behaviors and (n-6) PUFA-induced protein kinase C (PKC) activity in the brain. Three different strains of pregnant mice were fed isocaloric diets containing either 16% (control) or 43% (high) energy derived from fat high in (n-6) PUFA (corn oil: Balb/c and CD-1 mice, or soybean oil: C3H mice) throughout gestation. From birth onward dams and offspring were fed a nonpurified diet containing 12% energy from a variety of fats. Two- to 12-month-old female and male offspring of dams exposed to a high (n-6) PUFA diet during pregnancy were significantly more active in an open field, more aggressive in the resident-intruder test and spent less time immobile in the swim test than offspring of dams exposed to a control (n-6) PUFA diet. Significantly greater PKC activity in the hypothalamus and moderately less PKC activity in the whole brain (P = 0.10) were seen in the 2-month-old female and male high (n-6) PUFA offspring compared to controls. Our findings indicate that in utero exposure to a high (n-6) PUFA diet subsequently increases locomotor activity and aggression, and reduces immobility in the swim test. The mechanism mediating these effects may be linked to an increased PKC activity in the hypothalamus.     

Aging and time-of-day effects on cognition in rats.

This study used an animal model to investigate the importance of the time at which testing occurs for age differences in learning and memory. Groups of old and young rats were entrained to a 12-hr light–dark schedule and administered tests of delayed alternation and inhibitory avoidance conditioning at the beginning or end of their high-activity cycle. Apart from normal age differences in test performance, the behavioral results demonstrated that old but not young rats were affected by the time of testing. In both tasks, old rats tested late in the activity cycle performed significantly worse than did old rats tested early in the cycle, under conditions that challenged memory processes that are known to involve the hippocampus. The results indicate that circadian disruption in old age can adversely affect memory and related cognitive function, with important implications for inhibitory control. (PsycINFO Database Record (c) 2010 APA, all rights reserved)