D-cycloserine and early ethanol exposure in developing rats.

Pregnant rats were exposed to one of the following treatments: 20% aqueous sucrose (w/v; Control), 20% aqueous sucrose with 20 mg D-cycloserine (DCS), 20% aqueous sucrose with 5% ethanol (ETH), or 20% aqueous sucrose with both 20 mg DCS and 5% ethanol (DCS+ ETH). Treatments were delivered in 20 ml of drinking water provided daily, as pilot work had determined that this was the average daily water consumption for female rats. Treatments began on Day 10 or 11 of pregnancy and terminated on postnatal Day 10. As juveniles, offspring were tested for activity in an open field and motor coordination using a rotating rod. Ethanol and DCS+ Ethanol groups were the most active groups in the open field, and DCS and DCS+ Ethanol groups had fewer falls than the Control and Ethanol groups on the rod test. Results suggest that DCS might provide protection from ethanol's adverse effects on some developmental behaviors.

Prefrontal cortex lesions differentially disrupt cocaine-reinforced conditioned place preference but not conditioned taste aversion.

The reinforcing efficacy of cocaine is thought to involve, at least in part, mesocortical dopaminergic (DA) neurons. Rats will self-administer cocaine applied directly into the medial prefrontal cortex but not into nucleus accumbens or the ventral tegmental area (Goeders & Smith, 1983). The present experiments were conducted to assess whether lesions of prefrontal cortex (mesocortical DA target regions) attenuate the reinforcing properties of systemically administered cocaine. Male Sprague-Dawley rats were anesthetized, and one of three subfields (medial, orbital, or precentral) of the prefrontal cortex was removed by aspiration or no brain injury was done (sham operates). In four experiments the rats were tested on conditioned place preference (CPP), conditioned taste aversion (saccharin conditioned stimulus, cocaine unconditioned stimulus), general activity in the running wheel and open field, and food-reinforced spatial alternation in the T-maze. Sham operates demonstrated a cocaine-induced place preference, rats with medial frontal lesions showed a cocaine-induced place aversion, and other operates showed neither a conditioned place preference nor an aversion. The results of this experiment suggest that lesions of the DA projection fields of the prefrontal cortex in the rat reduce the positive reinforcing properties of systemically injected cocaine. In the second experiment, all subjects showed a conditioned taste aversion of equal magnitude. This suggests that whereas the positive reinforcing properties were affected differentially by prefrontal cortex lesions, the aversive properties were not affected. In Experiment 3 there were no lesion-induced differences in activity in either the running wheel or the open field. Therefore, changes in motor activity cannot account for the CPP data. In the final experiment, the medial frontal operates were impaired relative to the precentral and sham operates on learning to alternate choices in the T-maze, but the orbital frontal operates' performance was not different from that of any other group. This suggests that a general disruption of all reinforcement mechanisms did not occur following these lesions. Instead, these results indicate that mesocortical DA projection regions are involved with mediating the reinforcing properties of cocaine and that there is a separate system mediating the aversive properties of cocaine.

Progesterone facilitates the acquisition of avoidance learning and protects against subcortical neuronal death following prefrontal cortex ablation in the rat.

Following a cortical injury, neurons in areas near and connected to the site of injury begin to degenerate. The observed neuronal death may contribute to the severity of the observed behavioral impairments. The purpose of the present study was to examine if progesterone, a hormone known for its effectiveness at reducing cerebral edema, could protect against secondary neuronal death and facilitate the acquisition of an avoidance learning task in an ablation model of cortical injury. Rats served as sham controls or received bilateral ablation of the medial prefrontal cortex followed by a 10-day regimen of progesterone (4 mg/kg) or oil vehicle (1 ml/kg) beginning 1 h after cortical lesions. Progesterone-treated lesion rats showed a significant facilitation of avoidance learning compared to oil-treated lesion controls. In addition, progesterone-treated lesion animals did not differ from either progesterone- or oil-treated sham controls in avoidance learning. Anatomical analysis revealed that progesterone treatment decreased the amount of neuronal death seen in the striatum and the mediodorsal nucleus of the thalamus. The findings are consistent with the notion that progesterone is an effective neuroprotective agent and suggest that the hormone can reduce the behavioral impairments associated with frontal cortical ablation injury.

Pretest CS cueing facilitates the recovery of avoidance behavior following visual cortex lesions in the rat.

Rats were trained on a four-way shuttle box with a compound light-tone conditioned stimulus (CS) until they emitted 7 avoidance responses in 10 trials (7/10) prior to bilateral ablation of the visual cortex or sham surgery. On Day 5 after surgery, rats were cued with either the compound light-tone CS, the light or tone portion of the CS only, or had no exposure to the CS. On Day 10 after surgery, all animals were tested for avoidance retention under the same conditions as preoperative training. The findings indicate that following a lesion, cueing with the light-tone compound CS facilitates performance as does light alone. Cueing to the tone alone has no effect. In sham animals, only cueing with the light-tone CS was effective in enhancing avoidance retention. Results are interpreted as early and modality-specific sensory cueing may facilitate the recovery process.

Medial prefrontal lesion deficits involving or sparing the prelimbic area in the rat.

The rat medial prefrontal cortex (PFC) is believed to play a central role in working memory and selective attention processes. More recently, it has been shown that the effects of large PFC lesions on working memory may be due to the prelimbic area of the PFC. The aim of the present study was to compare the effects of lesions of the prelimbic area with PFC lesions that involved or spared the prelimbic area on shuttlebox avoidance and radial maze learning in rats. The findings indicate that rats with PFC lesions that spared the prelimbic area were impaired at avoidance but not radial arm maze learning, whereas rats with prelimbic lesions or PFC lesions that included this area were impaired on the radial arm maze but not the avoidance learning task. Results support the notion that the medial frontal cortex of the rat is a functionally dissociable region and suggest that the prelimbic area appears to be critical for working memory, but less so for attention processes.

Behavioral and neurochemical interactions of dextroamphetamine and methylphenidate in rats.

The effects of dextroamphetamine and methylphenidate on locomotor activity and brain levels of norepinephrine and dopamine were compared in male Sprague-Dawley rats. Both drugs produced a dose-related increase in locomotor activity during the hour immediately following intraperitoneal administration. However, combined administration of drugs elicited only the effect of dextroamphetamine. Brain levels of norepinephrine and dopamine also increased 1 hr after dextroamphetamine dosing. Methylphenidate did not exhibit these effects and antagonized the neurochemical changes produced by dextroamphetamine. Although both drugs are considered to exert their effects by indirect activation of brain catecholamine systems, differences in their mechanism of action appear to result in a lack of additive or antagonistic effects when dextroamphetamine and methylphenidate are coadministered. These findings may have clinical significance with respect to the use of such agents in minimal brain dysfunction.

Differences in placebo effects.

Constant volume injections of water and saline were evaluated in terms of their effects upon locomotor activity in the rat. Both solutions produced an overall decrease in activity and were found to be nonequivalent in their effect.

Role of the caudate nucleus in recovery from neonatal mediofrontal cortex lesions in the rat.

Ablation of medial prefrontal cortex impairs spatial discrimination learning in adult but not in neonatally lesioned rats. Orbital prefrontal cortex and adjacent convexity neocortex need not be left intact to observe this sparing of function. This study examined the possibility that the caudate nucleus, remaining intact after early medial prefrontal cortex lesions, might be involved in the observed behavioral sparing. Neonatal rats given combined lesions of the medial prefrontal cortex and head of the caudate nucleus were compared to age/litter-matched sham-operated controls on spatial alternation and place response acquisition and "reversal" tests. The results show that the performance of these neonatally lesioned subjects was deficient on both tests. The discussion centers on possible recovery mechanisms in rats given prefrontothalamic system damage early in life.

Disruption of neophobia, conditioned odor aversion, and conditioned taste aversion in rats with hippocampal lesions.

Previous studies have implicated the hippocampus in the acquisition of conditioned taste aversions. However, the effect of hippocampal (HPC) lesions on the acquisition of conditioned aversions to the distal olfactory cue has not been investigated. In this study rats with bilateral electrolytic hippocampal lesions were given access to an odor conditioned stimulus (CS) alone or a compound odor-taste CS, followed by an injection of LiCl or saline. The results indicated that HPC lesions attenuated the neophobic response to both CSs, and disrupted conditioned odor and taste aversions, relative to sham-operated controls. Furthermore, the disruption in conditioned odor aversions could not be attributed to attenuation of neophobia in lesioned subjects nor to prolonged neophobia in sham-operated controls. The results are consistent with pharmacological studies in suggesting that the hippocampus is involved in the formation of conditioned odor aversions.