The effects of lesions to the rat hippocampus or rhinal cortex on olfactory and spatial memory: retrograde and anterograde findings.

The role of the hippocampal system in retrograde and anterograde amnesia was investigated by using a novel olfactory-guided paradigm and a traditional test of spatial learning. In the retrograde study, rats were trained on a sequence of two-choice olfactory discriminations in the weeks prior to receiving neurotoxic lesions of the hippocampus or aspiration lesions of the perirhinal-entorhinal cortex. Memory tests for preoperatively learned discriminations revealed no statistical impairment for subjects with damage to the hippocampus on a problem learned remote in time from surgery (i.e., 4 weeks +) or on the two recently learned discriminations (i.e., 1-3 weeks prior to surgery). The performance of subjects with perirhinal-entorhinal damage provided an important comparison for subjects with specific hippocampal lesions. Despite showing intact memory for the remotely learned problem, perirhinal-entorhinal damage resulted in numerically (although not significantly) weaker performance on postoperative tests of retention for the discriminations learned in the 3 weeks prior to surgery. In the anterograde portion of the study, long-term memory for newly acquired discriminations was spared in subjects with damage to the hippocampus, whereas subjects in the perirhinal-entorhinal lesion group again showed the weakest memory performance on these tests of 5-day retention. Postoperative water maze learning was uniformly impaired in subjects with damage to the hippocampus and perirhinal-entorhinal cortex, thus confirming the effect of these lesions and supporting the involvement of these brain areas in spatial processes. These findings further dissociate the specific involvement of the hippocampus in tasks of a spatial-relational nature versus nonrelational tasks, such as discrimination learning and recognition memory (e.g., Duva et al., 1997; Eichenbaum, 1997; Eichenbaum, Schoenbaum, Young, & Bunsey, 1996). Moreover, the results suggest that damage to the hippocampus itself does not contribute to retrograde or anterograde memory impairments for all types of information, whereas the data suggest a more important role for the perirhinal-entorhinal cortex in recognition memory, irrespective of modality.

Differential effects of dorsal and ventral hippocampal lesions.

Several studies have demonstrated that dorsal, but not ventral, hippocampus is critical for spatial memory. The mnemonic role of the ventral hippocampus remains unclear. The existence of relatively direct connections between hypothalamic nuclei and ventral hippocampus suggests that the ventral hippocampus may be involved in acquisition of information regarding internal cues (e.g., hunger). Male Long-Evans rats received ibotenic acid-induced lesions of either dorsal or ventral hippocampus or underwent sham surgeries. After a 3 week recovery, subjects were tested on delayed alternation in a T-maze and on a task in which food-deprivation state was used as a contextual cue (Davidson and Jarrard, 1993). Rats with dorsal, but not ventral, lesions were impaired in delayed alternation, consistent with previous findings, but both groups were impaired in the learning of the internal state-shock association task.

Specific effects of idazoxan in a distraction task: evidence that endogenous norepinephrine plays a role in selective attention in rats.

Rats were injected with the alpha 2-adrenergic antagonist idazoxan (IDZ) prior to testing on vigilance and distraction tasks. In the vigilance task, rats responded with nose pokes to brief visual cues presented at variable intervals following trial onset. The distraction task was similar except that irrelevant odor cues (distractors) were presented in the interval prior to light onset on some trials. IDZ injection had no effect on performance in the vigilance task. In the distraction task, however, the higher IDZ dose (1.0 mg/kg) modulated the propensity to make a premature response when the distractors were presented. Notably, the direction of the effect varied with the rats' baseline level of distractibility. This pattern of effects suggests that endogenous norepinephrine (NE) influences distractibility and/or selective attention.

The catalepsy test: its ups and downs.

The typical catalepsy test consists of placing an animal into an unusual posture and recording the time taken to correct this posture. This time is regarded as an index of the intensity of catalepsy. Catalepsy is a robust behavior, and the lack of standardization does not usually hinder its actual detection. However, the intensity of the cataleptic effect is influenced by minor methodological differences, and thus interpretation and comparison of results across laboratories are difficult. The behavioral catalepsy test can use any of several different apparatus, including wire grids, parallel bars, platforms, or pegs, to situate the animals in unusual positions. The most common, however, is the "bar test," and despite its wide use in psychopharmacological research, even parameters of this test are not standardized. The present article reviews the wide variety of parameters chosen by investigators that measure catalepsy. The methodological issues of repeated testing, scaling of scores, apparatus, animal weight, maximal test duration, behavioral criteria, and other influences are discussed. In addition, a brief review of the neuropharmacological basis of catalepsy is also included. Finally, it is argued that a universal, standardized bar test be adopted by researchers. New data on a novel automated bar test in the Digiscan Activity Monitoring System is presented.

Regulatory changes following kainic acid-induced striatal lesions.

Kainic acid-induced lesions (KAL) of the striatum produce body weight and regulatory deficits in the rat. Unlike lateral hypothalamic rats. KAL rats drink more during food deprivation and eat more afterwards as compared to both baseline conditions and control rats. The present study investigated these effects further. As in previous studies, food deprivation was found to cause polydipsia and increased postdeprivational food intake in the KAL animal. Urination and defecation, often used as an index of emotionality, were also found to increase under these conditions. When the antidiuretic hormone vasopressin was injected, all of these differences remained with the exception of postdeprivational feeding--KAL rats no longer ate more than controls. These findings suggest that psychogenic factors--but not hormonal influences--may play a primary role in the regulatory peculiarities seen in the KAL rat.

The topography of the locomotor effects of haloperidol and domperidone.

The neuroleptics are currently the primary mode of treatment for schizophrenia. Unfortunately, the study of the behavioral effects of these drugs has been hampered by inadequate methodology. Researchers have lacked means sensitive enough to detect the neuroleptic's spontaneous behavioral effects at low doses. Consequently, most previous studies have measured the ability of these drugs to block the effects of various dopamine agonists. In an attempt to remedy this, the present study employed one of the recently developed automated animal activity monitors. This system was used to measure the spontaneous nocturnal behavioral effects of the neuroleptic haloperidol (0.0, 0.1, 0.5, 1.0 mg/kg) on 12 male Sprague-Dawley rats. The behavioral effects of domperidone (0.0, 0.1, 0.5, 1.0 mg/kg) were also studied in order to compare the effects of central and peripheral dopamine antagonism. The results showed that haloperidol depressed all aspects of behavior studied--even at the lowest dose--while domperidone depressed only average speed. These results suggest that all of the locomotor variables studied, save average speed, are centrally mediated. Average speed, though influenced by central mechanisms, seems primarily a peripheral function.