Circular Corridor Research Articles

Effects of early handling on amphetamine-induced locomotor activation and conditioned place preference in the adult rat.

Altered hormonal stress responsiveness has been implicated in psychostimulant responsivity, and early handling represents a mild environmental manipulation which alters the hormonal profile following stress exposure. The present experiments examined whether early handling in rats would alter locomotor effects of amphetamine, as well as cross-sensitization of locomotor responsiveness after chronic stress. Conditioned place preference (CPP) for amphetamine was also measured. Handling consisted of daily 15-min isolation periods from days 1-12 postnatally. Novelty- and amphetamine (0, 1.5 mg/kg)-induced locomotion were examined using circular corridors in adult rats that were either restrained repeatedly over 8 days or not disturbed prior to testing. The effects of handling on amphetamine (0, 1, 2, 5 mg/kg) conditioned place preference (CPP) were also examined following 3 days of drug-compartment pairings. Early handling produced a more rapid post-stress recovery in corticosterone levels. Handled animals also exhibited a significant attenuation in amphetamine-induced CPP compared to non-handled controls. Locomotor responsiveness to novelty and amphetamine was not altered by early handling. Although no cross-sensitization was observed, evidence for stress sensitization was seen, but was unaffected by early handling. Handled animals showed an attenuated CPP for amphetamine, data suggesting that sensitivity to the reward value of drugs of abuse in adulthood may be susceptible to relatively minor environmental manipulations early in life. This effect of handling on CPP does not seem to reflect differences in locomotor sensitivity to amphetamine.

α-Linolenic Acid Deficiency Modifies Distractibility but Not Anxiety and Locomotion in Rats during Aging

In rodents, chronic dietary α-linolenic acid deficiency decreases learning and memory and alters dopaminergic and serotoninergic neurotransmission. However, these two neurotransmitter systems are related mainly to attention, emotion and locomotion. Therefore, we decided to investigate the effects of dietary α-linolenic acid deficiency in rats tested with animal models of distractibility (the distractometer procedure), anxiety (the elevated plus maze) and ambulatory activity (a circular corridor). Moreover, because these neurochemical modifications persist during aging, we decided to study the effects of aging on these behaviors by using rats aged 2, 6, 12 and 24 mo. An age-related decline in distractibility was observed that was accelerated by linolenic acid deficiency. Indeed, an age-related reduction in distractibility was found in so far as distraction time was reduced at the age of 12 mo in controls and at the age of 24 mo in deficient groups compared with 2-mo-old rats. Moreover, distraction time was significantly lower in 6- and 24-mo-old rats fed a deficient diet compared with age-matched controls. Anxiety was not modified by diet or age. Finally, a parallel decrease in locomotion was exhibited by rats fed both diets between 6 and 12 mo of age. Locomotion was not modified by diet. These results show that dietary α-linolenic deficiency alters behavior in a very specific way; distractibility is modified by diet, whereas anxiety and locomotion are not, suggesting that particular brain areas may be altered.

Sex-linked behavioural differences in mice expressing a human insulin transgene in the medial habenula

We previously reported that a human insulin transgene was specifically expressed in the medial habenula of the adult mouse brain, and that this expression was ascribed to the Δ-168 transgene. The present study analyses the possible behavioural consequences of this insulin transgene expression using measures of food intake, spontaneous activity, emotional reactivity, learning and extinction performance of an operant task. The Δ-168 transgenic mice did not differ from the C57BL/6 control mice as concerns food intake, behaviour in the open field, or emotional response in an elevated plus maze. On the other hand, measures of locomotor activity in a circular corridor revealed a significantly faster decline of spontaneous locomotor activity in male as compared to female Δ-168 transgenic mice. Moreover, as compared to female transgenic mice, male transgenic mice exhibited a deficit in the rate of acquisition and an acceleration of the rate of extinction of a bar press response in a Skinner box. In contrast, the behaviour of female transgenic mice did not differ from either male or female C57BL/6 control mice. The results of the present study demonstrate that the behavioural modifications observed in Δ-168 transgenic mice are sex-linked and suggest that these behavioural differences result from changes in the interaction (interface) between motivational and motor mechanisms mediated via the striato-habenulo-mesencephalic system.

Reactivity to novelty during youth as a predictive factor of cognitive impairment in the elderly: a longitudinal study in rats

A life-span study of certain behavioral traits was conducted in rats. Animals were repeatedly tested in a circular corridor for reactivity to novelty and in a recognition memory task for cognitive abilities. These measures revealed important inter-individual differences in young as well as in old subjects. Some of these differences appear with aging (memory deficits) and others disappear (high reactivity to novelty). Moreover, a relationship between high reactivity to novelty in youth and deficits in memory recognition in elderly was found. Rats that are high-responders to novelty had age-related memory impairments whereas the low-responder rats did not. While the biological mechanism linking these two behavioral traits remains to be demonstrated, this study shows that age-related impairments can be predicted by factors detectable early in life.

Blockade of Prefronto‐cortical α1‐Adrenergic Receptors Prevents Locomotor Hyperactivity Induced by Subcortical D‐Amphetamine Injection

The stimulation of cortical dopaminergic D1 receptors can counteract the increased locomotor activity evoked by D-amphetamine application in the nucleus accumbens (Vezina et al., Eur. J. Neurosci., 3, 1001-1007, 1991). Moreover, an alpha 1 antagonist, prazosin, prevents the locomotor hyperactivity induced by electrolytic lesions of the ventral tegmental area (Trovero et al., Neuroscience, 47, 69-76, 1992). Attempts were thus made to see whether blockade of alpha 1-adrenergic receptors in the rat prefrontal cortex could reduce nucleus accumbens D-amphetamine-evoked locomotor activity. Rats implanted chronically and bilaterally with cannulae into the medial prefrontal cortex and the nucleus accumbens were used for this purpose and locomotor activity was monitored in circular corridors. Preliminary experiments indicated that intraperitoneal injection of prazosin (0.06 mg/kg) reduces the locomotor hyperactivity induced by the peripheral administration of D-amphetamine (0.75 mg/kg). This effect of prazosin was not observed when locomotor hyperactivity was obtained by an intraperitoneal injection of scopolamine (0.8 mg/kg). Bilateral nucleus accumbens injections of D-amphetamine (4.0 nmol/side) markedly increased locomotor activity, as estimated in a 30 min period. Prior (20 min) bilateral injections of either prazosin or WB-4101 (0.16 pmol) into the medial prefrontal cortex abolished the nucleus accumbens D-amphetamine-evoked response. The recovery of the nucleus accumbens D-amphetamine-evoked response was closely dependent on the amount of prazosin used, very prolonged inhibitory effects of the drug being seen with a high amount (> 4 days with 160 pmol). In contrast, whatever the amount of WB-4101 used (0.16-160 pmol), recovery occurred within 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolactin as a link between behavioral and immune differences between the Roman rat lines

Roman high (RHA)- and low (RLA)-avoidance rats are two lines of Wistar rats genetically selected on the basis of their active avoidance behavior in a shuttle-box. They also differ in several other behavioral responses, such as their locomotor activity in novel environments (open-field, circular corridor), with the RHA rats being more active than the RLA animals, as well as in endocrine reactivity and immune functions. These experiments were designed to investigate further the neuroendocrine characteristics of these animals as a possible link between the brain and immune functions. Despite the marked behavioral and immune differences observed, no between-lines variation could be found in basal hypothalamo-pituitary-adrenocortical axis activity or in its responses to different protocols of novel environment stress, or after corticotropin-releasing factor (CRF) challenge. On the other hand, stimulated prolactin levels were higher in the low avoidance line. These results exclude the pituitary-adrenocortical axis and suggest prolactin as a link between behavioral and immune differences between the Roman lines. Moreover, these results indicate that these rats may be an excellent model for the study of the relationships between the brain and the immune system.

Learning disturbances following excitotoxic lesion of cholinergic pedunculo-pontine nucleus in the rat

Compared to brain anterior cholinergic systems such as the septo-hippocampal and nucleus basalis-cortical pathways, posterior cholinergic groups have received little attention with respect to their involvement in learning and memory. In this study, the effect of lesion of the cholinergic pedunculo-pontine cell bodies (PPN) by the excitotoxin quisqualic acid was investigated on spontaneous locomotor activity and learning in rats. Behavioral tasks designed to test both reference memory (cross maze and water maze) or working memory (radial maze) were used. PPN lesion had no effect on initial nor on nocturnal locomotor activity in a circular corridor. The lesion disrupted learning in the water and radial mazes, but was without influence on acquisition in the cross maze. The difference in results obtained in the two tasks designed to test reference memory (cross maze and water maze) indicated that the disturbance depended on task difficulty rather than on a particular memory component. It is suggested that the PPN is involved in the sustained attention required to perform correctly in water and radial mazes. The PPN cannot therefore be considered as a uniquely extrapyramidal structure. In addition to its descending outputs, the PPN has ascending connections to the neocortex, either directly or indirectly via the thalamus, and so pathological changes in this region may be partly responsible for the cognitive disorders of aging or those observed in various neurodegenerative conditions.

Individual reactivity to novelty predicts probability of amphetamine self-administration

The present study demonstrates a relationship between individual responses to environmental activation, such as novelty, and propensity to acquire amphetamine self-administration. Locomotor activity cumulated over 2 h of exposure to a circular corridor was a stable and novelty-dependent feature of behaviour in individual rats. The differences between subjects in this behaviour were maintained over two trials at 1 month intervals, but disappeared over 4 days when the animals were tested daily, i.e. when the environment was no longer novel. The subjects with the higher locomotor response to novelty (HR group) also showed a higher propensity to acquire amphetamine self-administration, while the subjects with the lower response to novelty (LR group) did not acquire self-administration over 7 days of testing. Differences in self-administration of HR animals could not be accounted for by differences in exploratory behaviour. Thus, HR animals did not show higher investigative responses in a hole exploration test. Animals with the higher locomotor response to novelty also showed a greater release of corticosterone in the same environment. Since dopaminergic (DA) neurons are activated by both amphetamine and novelty, it is possible that differences in the propensity to acquire amphetamine self-administration may be accounted for by differences in the activity of DA neurons.

Individual reactivity to novelty predicts probability of amphetamine self-administration.

The present study demonstrates a relationship between individual responses to environmental activation, such as novelty, and propensity to acquire amphetamine self-administration. Locomotor activity cumulated over 2 h of exposure to a circular corridor was a stable and novelty-dependent feature of behaviour in individual rats. The differences between subjects in this behaviour were maintained over two trials at 1 months intervals, but disappeared over 4 days when the animals were tested daily, i.e. when the environment was no longer novel. The subjects with the higher locomotor response to novelty (HR group) also showed a higher propensity to acquire amphetamine self-administration, while the subjects with the lower response to novelty (LR group) did not acquire self-administration over 7 days of testing. Differences in self-administration of HR animals could not be accounted for by differences in exploratory behaviour. Thus, HR animals did not show higher investigative responses in a hole exploration test. Animals with the higher locomotor response to novelty also showed a greater release of corticosterone in the same environment. Since dopaminergic (DA) neurons are activated by both amphetamine and novelty, it is possible that differences in the propensity to acquire amphetamine self-administration may be accounted for by differences in the activity of DA neurons.

Locomotor activity in relation to dopamine and noradrenaline in the nucleus accumbens, septal and frontal areas: a 6-hydroxydopamine study.

Locomotor activity was automatically recorded in a circular corridor in rats treated with 6-hydroxydopamine in the ventral tegmental area (VTA), septum and frontal cortex. Control and experimental groups showed similar hyperlocomotor responses in the novel apparatus lasting 3 h. Circadian changes are described. VTA lesions resulted in increased dark activity and a large response to apomorphine compared to other lesion and control groups. Septal lesions did not affect locomotion. The frontal group showed a small increase of locomotion after apomorphine treatment that might reflect increased receptor sensitivity in cortical or subcortical areas. Together with correlations between motor activity and cortical levels of dopamine and noradrenaline these results are interpreted to support a role for dopamine, noradrenaline and the frontal cortex in modulating locomotion which is primarily mediated by VTA-accumbens-dopamine activity.

Locomotor hyperactivity and hypoexploration after lesion of the dopaminergic-A10 area in the ventral mesencephalic tegmentum (VMT) of rats

The lesion of the ventral mesencephalic tegmentum (VMT) and especially of the dopaminergic (DA) A10 neurons induced disturbances of spontaneous activity in the rat. Measured in different situations (circular corridor, open field, hole box), locomotor activity was dramatically and permanently increased (5 days of recording) without modifications of the circadian rhythm, although exploratory patterns of behavior were reduced. In contrast, the administration of a low dose of d-amphetamine (1 and 2 mg/kg i.p.) to naïve rats induced an increase of both locomotor and exploratory activities. A qualitative analysis of spontaneous activity of rats after VMT lesions and after administration of d-amph, revealed opposing aspects of behavior. Residual response to d-amph of VMT-lesioned rats suggest a subtotal destruction of DA-A10 neurons, the implication of an over activity of these remaining DA-A10 neurons on behavioral deficit is considered. Out results can be explained by a deficiency in attention processes.

Interactions between d-Ala-Met-enkephalin, A10 dopaminergic neurones, and spontaneous behaviour in the rat

We have investigated the interaction between opioid peptides and dopaminergic A10 (DA-A10) neurones in the ventral tegmental area (VTA). The behavioural consequences of VTA infusion of d-Ala-Met-enkephalinamide (DALA) were analyzed. DALA elicited a dose-dependent increase in locomotor activity measured in photocell cages and the circular corridor. Observations in the open field and in a hole box revealed thet DALA-induced behavioural stimulation was characterized by enhancement of locomotion, rearing, and number of hole visits, while grooming time and duration of hole visits were decreased. DALA-induced stimulation was reserved by naloxone, and was completely blocked by 6-OHDA destruction of DA-A10 terminals. d-Amphetamine-induced behavioural activation was potentiated by simultaneous VTA infusion

Interactions between d-Ala-Met-enkephalin, A10 dopaminergic neurones, and spontaneous behaviour in the rat**

We have investigated the interaction between opioid peptides and dopaminergic A10 (DA-A10) neurones in the ventral tegmental area (VTA). The behavioural consequences of VTA infusion of d-Ala-Met-enkephalinamide (DALA) were analyzed. DALA elicited a dose-dependent increase in locomotor activity measured in photocell cages and the circular corridor. Observations in the open field and in a hole box revealed thet DALA-induced behavioural stimulation was characterized by enhancement of locomotion, rearing, and number of hole visits, while grooming time and duration of hole visits were decreased. DALA-induced stimulation was reserved by naloxone, and was completely blocked by 6-OHDA destruction of DA-A10 terminals. d-Amphetamine-induced behavioural activation was potentiated by simultaneous VTA infusion

Disappearance of hoarding and disorganization of eating behavior after ventral mesencephalic tegmentum lesions in rats.

The effects of ventral mesencephalic tegmentum (VMT) radio-frequency lessions on spontaneous and complex behaviors, such as food hoarding and alimentary patterns, were investigated. Activity measures indicated that VMT lesions increased horizontal activity in a circular corridor as well as in an open field whereas vertical activity (rearing) was decreased. After 12 hr of food deprivation, food hoarding and alimentary patterns were evaluated in a square open field to which rats had free access from their home cage. Control rats hoarded food and had organized feeding behavior, but experimental rats did not hoard. Moreover, increasing the open-field illumination did not reverse this deficit. Similarly, the VMT lesion induced disruption of the adaptative alimentary behavior in response to food deprivation. A strong correlation was observed between hoarding scores and the extent of locomotor hyperactivity. These results are discussed in terms of a possible implication of limbic-midbrain mechanisms in which the meso-cortico-limbic dopaminergic A10 neurons originating in the VMT might have a primary role.

Behavioral effects of lesions in the A10 dopaminergic area of the rat

Experiments have been carried out with 150 rats in order to study some psychophysiological functions of the mesencephalocortico limbic dopaminergic A10 group. Lesions in the A10 area were made by using 6-hydroxydopamine (6-OHDA) local injections; 2 small volumes of injections were used at the same concentration (2 μg/ 1 μ1 or 1 μg/0.5 μ1). In a first experiment the effects of these two injections were tested on locomotor activity measured in a circular corridor, 10 and 30 days after surgery. Injections provoked hyperactivity, mainly during nocturnal basal activity periods, but not during initial exploratory activity periods. The larger the injection, the more important the hyperactivity was. The larger injections induced important food spillage evidenced through the wire floor of the home cage and perturbation in a passive avoidance learning. There was no change in body weight or in amount of ingested food. In a second experiment, the effects of local injection of 6-OHDA in the other CA structures of bundles situated in or near the ventral tegmental area were tested. Injections in the substantia nigra compacta, in the noradrenergic ventral bundle, in the dorsal periventricular system-tegmental radiations did not provoke locomotor hyperactivity. In a third experiment, a possible role of the median raphe (MR) nucleus in the A10-lesion induced hyperactivity was tested: first, radiofrequency MR lesions were made and no durable significant hyperactivity was recorded; secondly, 6-OHDA (1 μg/0.5 μ1) was injected into the A10 area and activity was measured 10 days later: these injections provoked significant hyperactivity during the nocturnal basal and the diurnal basal activity periods. It might be concluded that neither the neighbor CA fibers nor the MR were directly involved in the ventral tegmental — 6-OHDA lesions syndrome. Anatomical controls by using the Fink-Heimer silver impregnating method have demonstrated, first, that the 6-OHDA injections did not destroy fibers other than catecholaminergic and secondly, that the degenerations are found in the forebrain and cortical limbic A10 projections. Hypotheses are made about a possible general inhibitory role of the A10 in behavior, in the sense of selective and attentive arousal processes, often impaired in some mental illnesses.

Locomotor activity after various radiofrequency lesions of the limbic midbrain area in the rat evidence for a particular role of the ventral mesencephalic tegmentum

Radiofrequency lesions were made in each structure of the Limbic Midbrain Area (LMA) : Gudden nuclei, raphe nuclei, mesencephalic ventral tegmentum (VMT), and locomotor activity was measured in a circular corridor 10 and 30 days after surgery. The first hour of exploration, the nocturnal basal activity and the diurnal basal activity were distinguished. During the exploratory phase the Gudden nuclei and VMT lesions induced hyperactivity, while dorsal raphe lesions provoked significant hypoactivity; during the light period VMT lesions and, to a less extent, dorsal Gudden nucleus lesions provoked hyperactivity. From these results it is assumed that the VMT represents a specific part of the LMA, where lesions provoked the most important activity disturbances.