DSP4-induced two-way active avoidance impairment in rats: involvement of central and not peripheral noradrenaline depletion.

Effects of early stimulation and/or perinatal flumazenil on emotional behavior of two psychogenetically-selected rat lines with divergent emotionality profiles

Previous experiments on two-way active avoidance have shown conflicting results after nucleus basalis magnocellularis lesion: disrupting effects with electrolytic lesions and facilitative effects with excitotoxic lesions. To resolve this issue, in this experiment, Wistar rats received pre-training bilateral electrolytic or ibotenic acid lesions and were trained in a massed two-way active avoidance conditioning. In order to test the long-term retention of the learned response, one additional session was conducted 10 days after the acquisition. Results showed that whereas electrolytic lesions did not affect the acquisition, ibotenic acid lesions enhanced it. Retention of active avoidance response was impaired by both electrolytic and ibotenic lesions of the NBM. These results suggest a role of the NBM in the memory consolidation and/or retrieval of two-way active avoidance.

Effects of different handling-stimulation procedures and benzodiazepines on two-way active avoidance acquisition in rats

Effects of infant and adult amygdaloid lesions upon acquisition of two-way active avoidance by the adult rat: Influence of rearing conditions

Lesioning of the rat basal forebrain leads to memory impairments in passive and active avoidance tasks

Active and passive avoidance following the administration of systemic DSP4, xylamine, or p-chloroamphetamine

Differential Effects of Prenatal Stress in Two Inbred Strains of Rats

Effects of electrical stimulation of the nucleus basalis on two-way active avoidance acquisition, retention, and retrieval

Many animal and human subjects can learn to avoid punishment or noxious stimuli by exploiting the sensory cues predicting them. In cue-signaled active avoidance (AA) learning, subjects first learn about the predictive properties of cues and subsequently learn a behavioral strategy of an avoidance response (e.g., crossing a hurdle that divides a two-compartment cage in order to avoid a mild but unpleasant footshock). AA learning develops with fear reduction as an intervening variable (Mowrer and Lamoreaux, 1946; Miller, 1948). If execution of avoidance action occurs on the pursuit of seeking safety, an overlap of recruitments of neurocircuitry essential for reward processing and for avoidance can be expected on the basis of two-process theory. Recent insights from two-way AA (2WAA) studies, which integrate both Pavlovian and instrumental components, provide strong evidence for the recruitment of emotional circuitry centered on the amygdala and motivational circuitry centered around midbrain dopaminergic structures. In this review, we address the following: (1) the role of emotional neurocircuitry in the formation of AA, (2) the involvement of reward circuitry and its input-output pathways on AA, and (3) the possible serial and parallel processing within and between these circuitries.

The effectiveness of neuroleptics in disrupting conditioned active avoidance has led to the widespread use of this test as an index of antipsychotic efficacy, whereas the tendency for these drugs to induce catalepsy is believed to reflect their propensity to cause extrapyramidal motor side-effects. Although the typical neuroleptic haloperidol produces catalepsy as well as profound deficits in conditioned active avoidance, the atypical neuroleptic clozapine does not induce catalepsy and is less effective than haloperidol in disrupting active avoidance. Furthermore, clozapine pretreatment prevents haloperidol-induced catalepsy. We investigated whether clozapine pretreatment might also reduce the disruptive effects of haloperidol on two-way active avoidance. We assessed the avoidance acquisition of the following drug treatment groups in which all animals received two injections prior to testing: vehicle + vehicle, vehicle + haloperidol (0.1 mg/kg, i.p.), clozapine (2.5, 5.0 or 10 mg/kg, i.p.) + haloperidol (0.1 mg/kg, i.p.), or clozapine (2.5, 5.0 or 10 mg/kg, i.p.) + vehicle. Haloperidol-pretreated animals showed markedly impaired active avoidance, deficits which were improved by 2.5 and 5 mg/kg but not by 10 mg/kg clozapine pretreatment. These data suggest that the disruptive effects of haloperidol on conditioned active avoidance partially mirror its capacity to induce catalepsy and extrapyramidal motor symptoms. Furthermore, this study indicates that clozapine may be effective in reducing motor side-effects caused by typical neuroleptics.

Limbic Structures and Behavior: Endocrine Correlates

The effects of excitotoxic lesion of the medial prefrontal cortex on latent inhibition, prepulse inhibition, food hoarding, elevated plus maze, active avoidance and locomotor activity in the rat

To investigate the effect of epimedium total flavone capsules on post-stroke cognitive impairment(PSCI) in rats. The transient middle cerebral artery occlusion(tMCAO) model was constructed on selected rats, and rats with impaired neurological function were randomly divided into the model group, low, middle, and high dose groups of epimedium total flavone capsules, and nimodipine tablet group. The cognitive function of rats was measured after administration. Pathological changes in brain tissue were observed after hematoxylin-eosin staining(HE). Neuronal nuclei(NeuN) and glial fibrillary acidic protein(GFAP) distribution in brain tissue were tested by immunofluorescent staining. The level of amyloid beta 1-42(Aβ_(1-42)), neuron specific enolase(NSE), acetylcholine(ACH), dopamine(DA), 5-hydroxytryptamine(5-HT), norepinephrine(NE), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and hypersensitive C-reactive protein(hs-CRP) in rat serum was tested. Moreover, Western blot was utilized to test the expression of nuclear factor-kappaB(NF-κB), p-NF-κB, alpha inhibitor of NF-κB(IκBα) protein, and p-IκBα protein in the hippocampus. The experimental results showed that epimedium total flavone capsules can improve the cognitive function of model rats, and the mechanism may be related to the regulation of the expression of p-IκBα and p-NF-κB proteins, so as to inhibit inflammatory response induced by ischemia-reperfusion.

Retrosplenial cortex lesions impair acquisition of active avoidance while sparing fear-based emotional memory

The effects of noradrenaline (NA) depletion upon amphetamine-induced hyperactivity were examined in five experiments. Central NA depletion via either systemic DSP4 or neonatal 6-OHDA antagonised the amphetamine-induced (2 mg/kg SC) increase in rearing behaviour, whereas lesions of the dorsal noradrenergic bundle using 6-hydroxydopamine antagonised the increase in locomotor activity. Peripheral NA depletion following systemic 6-hydroxydopamine to adult rats did not cause any changes in motor activity after acute amphetamine administration. Desipramine, the selective NA uptake inhibitor, blocked the effects of DSP4 upon amphetamine-induced rearing. NA depletion antagonised hyperactivity produced by the 2 mg/kg dose of amphetamine, but not the hyperactivity (rearing or locomotion) effects of amphetamine at 1, 4 or 8 mg/kg.