Footshock In Rats Research Articles

Contextual exploration previous to an aversive event predicts long-term emotional consequences of severe stress

Traumatic stress can lead to long-term emotional alterations, which may result in Posttraumatic Stress Disorder (PTSD). Fear reactions triggered by conditioned cues and exacerbated emotional arousal in face of non-conditioned stimuli are among the most prominent features of PTSD. We hypothesized that long-term emotional alterations seen in PTSD may depend on the strength of context-trauma association. Here, we investigated the contribution of previous contextual exploration to the long-term emotional outcomes of an intense foot shock in rats. We exposed male Wistar rats to a highly stressful event (foot shock, 2 mA, 1 sec) allowing them to explore or not the chamber prior to trauma. We, then, evaluated the long-term effects on emotionality. Fear was assessed by the time spent in freezing behavior either upon re-exposure to trauma context or upon exposure to an unknown environment made potentially more aversive by presentation of an acoustic stimulus. Behaviors on the elevated-plus-maze and acoustic startle response were also assessed. The possibility to explore the environment immediately before the aversive event led to differential long-term emotional effects, including a heightened freezing response to re-exposure to context, blunted exploratory behavior, fear sensitization and exacerbation of the acoustic startle response, in contrast to the minor outcomes of the foot shock with no prior context exploration. The data showed the strong contribution of contextual learning to long-term behavioral effects of traumatic stress. We argue that contextual representation contributes to the robust long-term behavioral alterations seen in this model of traumatic stress.

The effect of the steroid sulfatase inhibitor (p-O-sulfamoyl)-tetradecanoyl tyramine (DU-14) on learning and memory in rats with selective lesion of septal–hippocampal cholinergic tract

Dehydroepiandrosterone sulfate (DHEAS), is an excitatory neurosteroid synthesized within the CNS that modulates brain function. Effects associated with augmented DHEAS include learning and memory enhancement. Inhibitors of the steroid sulfatase enzyme increase brain DHEAS levels and can also facilitate learning and memory. This study investigated the effect of steroid sulfatase inhibition on learning and memory in rats with selective cholinergic lesion of the septo-hippocampal tract using passive avoidance and delayed matching to position T-maze (DMP) paradigms. The selective cholinergic immunotoxin 192 IgG-saporin (SAP) was infused into the medial septum of animals and then tested using a step-through passive avoidance paradigm or DMP paradigm. Peripheral administration of the steroid sulfatase inhibitor, DU-14, increased step-through latency following footshock in rats with SAP lesion compared to both vehicle treated control and lesioned animals (p<0.05). However, in the DMP task, steroid sulfatase inhibition impaired acquisition in lesioned rats while having no effect on intact animals. These results suggest that steroid sulfatase inhibition facilitates memory associated with contextual fear, but impairs acquisition of spatial memory tasks in rats with selective lesion of the septo-hippocampal tract.

Repeated exposure to immobilization or two different footshock intensities reveals differential adaptation of the hypothalamic–pituitary–adrenal axis

Factors involved in adaptation to repeated stress are not well-characterized. For instance, acute footshock (FS) of high intensity appears to be less severe than immobilization (IMO) in light of the speed of post-stress recovery of the hypothalamic-pituitary-adrenal (HPA) axis and other physiological variables. However, repeated exposure to IMO consistently resulted in reduction of the HPA response to the same stressor (adaptation), whereas failure to adapt has been usually reported after FS. Thus, in the present work we directly compared the activation of HPA axis and other physiological changes in response to both acute and repeated exposure to IMO and two intensities of FS (medium and high) in adult male rats. Control rats were exposed to the FS boxes but they did not receive shocks. Daily repeated exposure to IMO resulted in significant adaptation of the overall ACTH and corticosterone responses to the stressor. Such a reduction was also observed with repeated exposure to FS boxes and FS-medium, whereas repeated exposure to FS-high only resulted in a small reduction of the corticosterone response during the post-stress period. This suggests that some properties of FS-high make adaptation to it difficult. Interestingly, overall changes in food intake and body weight gain throughout the week of exposure to the stressors reveal a greater impact of IMO than FS-high, indicating that factors other than the intensity of a stressor, at least when evaluated in function of the above physiological variables, can influence HPA adaptation. Since FS exposure is likely to cause more pain than IMO, activation of nociceptive signals above a certain level may negatively affect HPA adaptation to repeated stressors.

Altered neuropeptide Y and neurokinin messenger RNA expression and receptor binding in stress-sensitised rats

A single session of footshocks in rats causes long-lasting sensitisation of behavioural, hormonal and autonomic responses to subsequent novel stressful challenges as well as altered pain sensitivity. These changes mimic aspects of post-traumatic stress disorder in humans. Our aim was to identify neuropeptide substrates in the central nervous system involved in stress sensitisation. Male Wistar rats were exposed to ten footshocks in 15 min (preshocked) or placed in the same cage without shocks (control). Two weeks later, rats were placed in a novel cage, subjected to 5 min of 85 dB noise, and returned to their home cage. Rats were killed either before or 1 h after noise and their brains processed for in situ hybridization for neuropeptide Y (NPY) and beta-preprotachykinin-I (PPT) mRNA. Additional groups of rats were killed under basal conditions and brains processed for NPY and neurokinin receptor binding with radiolabelled ligands. Two weeks after footshock treatment NPY mRNA expression was increased in the basolateral amygdala and showed preshock × noise interaction in the locus coeruleus (down after noise in controls, lower basal and unchanged after noise in preshocked). PPT expression in the lateral parabrachial nucleus also showed preshock × noise interaction (up after noise in controls, higher basal and down after noise in preshocked), and was increased after noise in the periaquaeductal grey. NK1 receptor binding in the agranular insular cortex and arcuate nucleus of the hypothalamus and NK2 receptor binding in the amygdala was lower in preshocked rats than in controls. Altered expression of NPY in the basolateral amygdala and locus coeruleus could contribute to or compensate for behavioural and autonomic sensitisation in preshocked rats. Altered PPT expression in the parabrachial nucleus may be involved in the altered pain processing seen in this model. Lower NK1 and NK2 receptor numbers in cortex, hypothalamus and amygdala may reflect secondary adaptations to altered neuropeptide release. These long-term changes in brain neuropeptide systems could offer novel leads for pharmacological modulation of long-term stress-induced sensitisation.

Involvement of group II metabotropic glutamate receptors in stress-induced behavioural sensitization

A short session of repeated foot shocks in rats causes long-lasting sensitization of behavioural, hormonal and autonomic responses to novel stressful challenges. The behavioural sensitization can be reduced by anxiolytics and mimics aspects of stress-induced changes in patients with post-traumatic stress disorder. The aim of this study was to test the efficacy of a group II metabotropic glutamate receptor (mGluR) agonist and assess altered brain mGluR receptor expression in shock-sensitized rats. Male Wistar rats were exposed to a 15-min session with ten 6-s foot shocks (preshocked). One and 2 weeks later, rats were intraperitoneally injected with the group II metabotropic glutamate receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) or vehicle, and 30 min later exposed to 5 min of 85 dB noise. For in situ hybridization with probes for mGluR1, mGluR2, mGluR3 and mGluR5, preshocked and control rats were killed under basal conditions 2 weeks after foot shocks and their brains cryosectioned. APDC had no clear effect in controls, but dose-dependently reduced high immobility and increased low locomotion and rearing seen in preshocked rats to the levels of controls. mGluR3 expression was increased in the basolateral nucleus of the amygdala, and mGluR2 expression was increased in the agranular insular cortex of preshocked rats compared to controls. Shock-induced behavioural sensitization in rats is reduced by acute treatment with a group II metabotropic glutamate receptor agonist. This effect may depend on the increased expression of amygdala mGluR3, which could be hypothesized as an endogenous mechanism to counteract stress-induced neuronal sensitization.

Individual reactivity to the open-field predicts the expression of cardiovascular and behavioural sensitisation to novel stress

Posttraumatic stress disorder (PTSD) is the fourth most common psychiatric disorder. It is associated with cardiovascular disorders and irritable bowel syndrome (IBS). Besides stressful life-events, a prior history of gastrointestinal infection is a predisposing factor for the development of IBS. Only a proportion of persons exposed to traumatic events develop PTSD. Several factors, like genetic predisposition, stressor intensity, cognitive appraisal mechanisms and coping processes influence the likelihood of developing PTSD after exposure to a trauma. We used a single session of footshocks in rats, an animal model with a high degree of validity for PTSD, to study whether transient colonic inflammation alters local and distal visceral sensitivity, and whether reactivity to the open-field (low (LA) or high (HA) active) predicts long-term stress-induced behavioural and cardiovascular sensitisation and altered visceral pain sensitivity. A distention series and noise challenge were given 2 weeks after foot-shocks, followed by a transient colonic inflammation period and a second distention series and noise challenge 4 weeks after foot-shocks. During exposure to noise, both before and after inflammation, footshocked rats showed increased immobility compared to controls, which was significantly greater in LA rats than in HA rats. LA preshocked rats also showed a greater blood pressure response to the noise test, but this only became evident in the second noise-test. Neither footshocks nor colonic inflammation affected duodenal pain sensitivity. The results provide additional evidence for long-lasting cardiovascular hyperresponsivity after a stressful event and indicate that its degree is predicted by personality traits or coping style.

Individual reactivity to the open-field predicts the expression of stress-induced behavioural and somatic pain sensitisation

Posttraumatic stress disorder (PTSD) is the fourth most common psychiatric disorder. It is associated with somatic complaints like pain problems. Only a proportion of persons exposed to traumatic events develop PTSD. Several factors, like genetic predisposition, stressor intensity, cognitive appraisal mechanisms and coping processes influence the likelihood of developing PTSD after exposure to a trauma. We used a single session of footshocks in rats, an animal model with a high degree of validity for PTSD, to study whether individual behavioural traits predict long-term stress-induced sensitisation of behavioural responsivity and somatic pain sensitivity and therefore can act as a vulnerability factor. Rats were selected for low (LA) and high (HA) open-field locomotor reactivity and then underwent a single session of footshocks. Two to 5 weeks after footshocks, behavioural sensitisation was investigated using a noise challenge, an electrified prod challenge and a forced swim test. Somatic pain sensitivity was measured using a tail-immersion test. During exposure to noise in a novel cage, footshocked rats showed increased immobility compared to controls, which was significantly greater in LA than in HA rats. Footshocked rats showed increased burying in the electrified prod challenge and no effect was found in the forced swim test. Footshocks caused hyperalgesia in LA rats, but hypoalgesia in HA rats. We conclude that low open-field locomotor reactivity predicts the degree of stress-induced behavioural sensitisation and the direction of altered somatic pain sensitivity, suggesting that an anxiety-prone personality or passive coping style may increase the risk of developing stress-related psychosomatic disorders.

Disruption and potentiation of latent inhibition by risperidone: the latent inhibition model of atypical antipsychotic action.

Latent inhibition (LI), that is, retarded conditioning to a stimulus following its nonreinforced pre-exposure, is impaired in some subsets of schizophrenia patients and in amphetamine-treated rats. Potentiation of LI by antipsychotic drugs (APDs) given in conditioning, under conditions that do not lead to LI in controls, is a well-established index of antipsychotic activity. Recently, we have shown that the atypical APD, clozapine, in addition disrupts LI if administered in pre-exposure, under conditions that lead to LI in controls. This study demonstrates the same behavioral profile for the atypical APD risperidone. LI was measured in a thirst-motivated conditioned emotional response procedure by comparing suppression of drinking in response to a tone previously paired with a foot shock in rats that received nonreinforced exposure to the tone prior to conditioning (pre-exposed (PE)) and rats for whom the tone was novel (non-pre-exposed (NPE)). We show that under conditions that did not yield LI in vehicle controls (40 pre-exposures and five conditioning trials), risperidone (0.25, 0.5, and 1.2 mg/kg) led to LI when administered in conditioning. Under conditions that led to LI in vehicle controls (40 pre-exposures and two conditioning trials), risperidone (0.25, 0.5, and 2.5 mg/kg) abolished LI when administered in pre-exposure; the latter effect was not evident with haloperidol. In addition, the effects of risperidone administered in both the pre-exposure and conditioning stages were dose-dependent so that the pre-exposure-based action was manifested at lower but not at higher doses. It is concluded that atypical APDs exert in the LI model a dual pattern of effects, which enables detection of their 'typical' action (conditioning-based LI potentiation) as well as a dissociation from typical APDs by their 'atypical' action (pre-exposure-based LI disruption). It is suggested that the former and latter effects are subserved by D2 and 5HT2A antagonism, respectively.

Involvement of corticotropin-releasing factor in the retrieval process of fear-conditioned ultrasonic vocalization in rats

The role of the corticotropin-releasing factor (CRF) system in the fear-conditioned ultrasonic vocalizations (USVs) induced by foot shocks in rats was investigated. In the acquisition phase of fear conditioning, the intracerebroventricular administration of CRF receptor antagonist α-hCRF attenuated USV responses related to context memory. Even after experiencing eight consecutive days of foot-shock challenges, the α-hCRF group emitted similar number of USVs as the control group if they were not given the drug. After the conditioning phase, the groups treated with α-hCRF or CRF receptor 1 (CRFR1) antagonist CP-154,526 emitted fewer conditioned USVs than the control group, although there was no difference in the USVs after the shock, which reflected physical stress. These results suggest that the central CRF systems, especially those mediated via CRFR1, are involved in the retrieval process, but not the acquisition or retention processes, of fear-related memory.

Angiotensin AT 2 receptors mediate vasodepressor response to footshock in rats : Role of kinins, nitric oxide and prostaglandins

Footshocks increased mean arterial pressure and heart rate. Systemic administration of losartan, a specific angiotensin AT 1 receptor antagonist, not only inhibited the pressor response to footshocks, but also resulted in vasodepression. Administration of 1-[[4-(dimethylamino)3-methylphenyl]methyl]-5 (diphenylacetyl)-4,5,6,7-tetrahydro-1 H imidazol (4,5- c] pyridine-6-carboxilic acid, ditrifluoro acetatemonohydrate (PD 123319), a specific angiotensin AT 2 receptor antagonist, did not alter the hemodynamic response to footshocks. Simultaneous blockade of angiotensin AT 1 and AT 2 receptors by combined administration of losartan and PD 123319, eliminated the vasodepressor response to footshocks unmasked in losartan-pretreated rats. Saralasin, a non-specific angiotensin receptor antagonist, abolished the cardiovascular response to footshocks similarly like the losartan+PD 123319 treatment. Our data suggest that the vasodepressor response to footshocks in the presence of an angiotensin AT 1 receptor antagonist is triggered by activation of angiotensin AT 2 receptors. We studied the role of kinins, nitric oxide and prostaglandins in the vasodepressor response observed after footshocks. The decrease in mean arterial pressure observed after footshocks in losartan-treated rats was blunted by icatibant (HOE 140), N G-nitro- l-arginine-methyl ester ( l-NAME) or indomethacin, indicating that kinins, nitric oxide and prostaglandins appear to be involved in the pressure response to footshocks during angiotensin AT 1 receptor blockade.

Differential profiles of nitric oxide and norepinephrine releases in the paraventricular nucleus region in response to mild footshock in rats

The purpose of this study was to determine whether the application of mild intermittent footshock stress can cause changes in the nitric oxide (NO) and norepinephrine (NE) releases in the hypothalamic paraventricular nucleus (PVN) region and medial prefrontal cortex (mPFC). Extracellular levels of NO metabolites and NE in the PVN region and mPFC were determined using an in vivo brain microdialysis technique in conscious rats. In the PVN region, we demonstrated that perfusion of N-methyl- d-aspartate through a microdialysis probe resulted in a dose-dependent increase in NO metabolite levels, whereas intraperitoneal administration of N G-nitro- l-arginine methyl ester produced a dose-dependent reduction in the levels of NO metabolites. The levels of NO metabolites in the PVN region increased after intraperitoneal administration of interleukin-1β in a dose-dependent manner, as we previously reported. This increase in NO metabolite levels was abolished 60 min after systemic administration of N G-nitro- l-arginine methyl ester compared to the vehicle-treated control group. Twenty minutes of intermittent footshock induced NE release but did not induce NO release in the PVN region. On the contrary, in the mPFC, 20 min of intermittent footshock induced both NO and NE releases. The present results reveal different patterns and time courses in NO and NE releases between the PVN region and the mPFC in response to mild intermittent footshock stress. These findings are likely to have helpful suggestions for our understanding of the hypothalamic–pituitary–adrenal axis and the limbic forebrain system response to different kinds of stress.

Brain AT 2 receptor mediate vasodepressor response to footshocks: Role of kinins and nitric oxide

In the present study the role of brain AT 2 receptor in the cardiovascular response to stress was investigated in conscious rats. Footshock-stress increased mean arterial pressure (MAP) and heart rate ( p < 0.0001). Intracerebroventricular (i.c.v.) administration of losartan (100 μg/5 μl), a specific angiotensin AT 1 receptor antagonist, not only attenuated the pressor response to footshocks, but also resulted in a consistent vasodepressor response (−10 mmHg, p < 0.02). Meanwhile, heart rate response was not altered. Given alone, PD 123319 (3 μg/5 μl, i.c.v.), a specific angiotensin AT 2 receptor antagonist, did not alter the hemody-namic response to footshocks. However, simultaneous block of brain AT 1 and AT 2 receptors by combined administration of losartan and PD 12319, eliminated the vasodepressor response unmasked after footshocks in rats i.c.v.-pretreated with losartan alone. In addition, we studied the role of brain kinins and nitric oxide (NO) in the vasodepressor response observed after footshocks in losartan i.c.v.-treated rats. Intracerebroventricular administration of icatibant (20 pmol/5 μl), a selective B 2 receptor antagonist, or N G-nitro- l-arginine methyl ester (100 μg/5 μl), a selective NO-synthase inhibitor, abolished the vasodepressor response to footshocks in losartan-treated rats. Our data suggest that the vasodepressor response to footshocks in the presence of AT 1 antagonist is triggered by activation of AT 2 receptor. Brain NO and kinins appear to contribute in this effect.

Effect of prenatal stress on plasma corticosterone and catecholamines in response to footshock in rats

WEINSTOCK, M.; POLTYREV, T.; SCHORER-APELBAUM, D.; MEN, D.; AND MCCARTY, R. Effect of prenatal stress on plasma corticosterone and catecholamines in response to footshock in rats. PHYSIOL BEHAV 64(4) 439–444, 1998.—The effect of prenatal stress was investigated on the sympathoadrenal response to novelty and footshock by measuring the time course of the changes in circulating corticosterone (COR) catecholamines and their metabolites. Pregnant rats were subjected to noise and light stress, three times weekly on an unpredictable basis throughout gestation. When the male offspring of stressed rats (PS) and those of unstressed mothers (C) were 4.5–5 months of age, they were prepared with indwelling catheters in the tail artery 24 h before the experiment. Resting levels of plasma COR, noradrenaline (NA), adrenaline (AD), dihydroxyphenylglycol (DHPG), dihydroxyphenylacetic acid (DOPAC), and dihydroxyphenylalanine (DOPA) were measured. Further blood samples were taken within 3 min of their transfer to the shock box, 1–2, 5, 15, and 45 min after footshock. Plasma COR was significantly higher in PS than in C rats at rest, but those of adrenaline, NA, and their metabolites did not differ in the two groups. Transfer of the rats to the shock box increased plasma COR, NA, adrenaline, and dihydroxyphenylglycol in both groups, and dihydroxyphenylalanine and dihydroxyphenylacetic acid only in PS rats. All the catechols increased further 2–3 min after footshock, except dihydroxyphenylalanine in PS rats. Plasma NA and dihydroxyphenylglycol levels were significantly higher in PS than in C rats immediately after footshock, indicating a greater activation of the sympathetic nervous system in PS rats. The findings demonstrate for the first time that prenatal stress can induce long term changes in the sensitivity of the sympathoadrenal system to stress.

The effect of oxcarbazepine on behavioural despair and learned helplessness.

The effect of oxcarbazepine was evaluated in two tests of depression (forced swimming and learned helplessness) and in the open-field test. Acute (three times over 24 h) oxcarbazepine 80 mg/kg (but not 40 mg/kg) decreased immobility time in the forced swimming test. In the learned helplessness test, 4 days of treatment with oxcarbazepine 80 mg/kg reversed the deficits induced by foot-shock in rats submitted to the two-way active avoidance test. Oxcarbazepine 80 mg/kg did not modify the behaviour of rats in the open-field test, an indication that, at this dose, oxcarbazepine did not show a locomotor stimulatory effect. Thus, the data of the present study suggest that oxcarbazepine has a potential antidepressive effect.

Emergent properties following brain injury: the claustrum as a major component of a pathway that influences nociceptive thresholds to foot shock in rats.

Flinch (pain) thresholds for electric current delivered to the feet were correlated with the amount of necrosis within the diencephalon and telencephalon for rats in which seizures had been induced by lithium and pilocarpine about two months before the testing. The shared variance of the quantitative damage within the claustrum, the anterior part of the paraventricular nucleus of thalamus, (central) mediodorsal thalamus, and lateral amygdala (ventromedial part) explained 81% of the variance in the nociceptive (flinch) thresholds. A primary role of the claustrum within the neuropathways that mediate the response to the interoceptive and "painful" characteristics of stimuli is indicated. The concept of primary pathways versus "emergent" pathways subsequent to excitotoxic damage within the neuromatrix is discussed.

Effects of central administration of arginine-vasopressin on aversive memory retrieval

This study examined whether arginine-vasopressin (A-VP), given before the test would produce an improved retrieval of aversive memory, in the same way as pre-exposure to inescapable footshocks, in rats. For this purpose animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were administered (intracerebroventricular) a single dose of 2.5, 5, 10 or 20 ng/rat of A-VP, 20-min before testing. In the retention test conducted with the same training apparatus 72 h after conditioning, the peptide treated rats showed a dose-dependent increase in latencies to enter the previously shocked goalarm, with the absence of such a difference in responding to the non-shocked goalarm. This differential response was not observed in saline treated rats. This effect of peptide on memory retrieval was similar to that seen following inescapable footshock in rats. These results suggest the possible involvement of central vasopressinergic mechanisms in the differential enhancement of memory of helplessness condition.

Effects of ACTH and ACTH 4-10 on aversive memory retrieval in rats.

The aim of the study was to examine whether ACTH and ACTH-fragment 4-10, given before the test would produce a selectively enhanced retrieval of aversive memories, in the same way as preexposure to inescapable footshocks, in rats. For this purpose animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were administered (s.c.) a single dose of 10, 20 or 40 ug/rat of ACTH or 5, 10 or 20 ug/rat of ACTH-fragment 4-10, 20-min before testing. The retention test conducted in the same training apparatus 72-hrs after conditioning showed a dose-dependent increase in latencies to enter the previously shocked goalarm with the absence of such a difference in responding to the nonshocked goalarm, in ACTH and ACTH 4-10 treated groups. This differential response was not observed in saline treated rats. This effect of peptides on memory retrieval was similar to that seen following inescapable footshock in rats. The results suggest the possible involvement of ACTH in the differential enhancement of memory of helplessness condition.

Amino acids, serotonin, and 5-hydroxyindoleacetic acid following foot shock in rats

Concentrations of tryptophan, serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in brain and plasma, as well as plasma amino acid composition, were measured after 1-h foot shock. Stress induced a rise in both plasma and brain 5-HIAA, whereas 5-HT concentration was found to be increased only in plasma. A prominent rise in brain tryptophan was observed, whereas in plasma, foot shock caused a significant increase only in tryptophan level. Concentrations of other amino acids were found to be either decreased or unchanged. Ratio of tryptophan to the other long-chain neutral amino acids increased significantly following foot shock. It is possible that stress-related changes in 5-HT turnover are due to increased plasma tryptophan, in turn causing a rise in brain tryprophan, necessary to cope with enhanced 5-HT metabolism, reflected as a rise in 5-HIAA levels.

Substance P is involved in the sensitization of the acoustic startle response by footshocks in rats

The acoustic startle response (ASR) can be enhanced by administration of footshocks (sensitization). The neural mechanisms underlying this effect are largely unknown. A previous electrophysiological study (Kungel et al., Brain Res., 643 (1994) 29–39) has shown that the neuropeptide substance P (SP) increases the responsiveness to acoustic stimuli of neurons in the caudal pontine reticular nucleus (PnC). Since the PnC is an important part of the primary acoustic startle circuit, we hypothesized that SP is involved in the enhancement of the ASR by electric footshocks. We tested this hypothesis in different experiments by locally injecting SP and SP-antagonists into the PnC of freely moving rats. The present data show that SP (0.5 pmol–1 nmol) locally injected into the PnC dose-dependently increases the amplitude of the ASR in rats. This effect was antagonized by pretreatment with the SP-antagonist CP-96,345. Furthermore, we show that the sensitization of the ASR by 0.6 mA-footshocks can be blocked by local microinjections of the SP-antagonists CP-96,345 (5 pmol–10 nmol) or CP-99,994 (0.5 nmol–100 nmol) into the PnC. Possible pathways relevant for the sensitization of the ASR are discussed.

Effects of the neuroleptic α-flupenthixol on latent inhibition in aversively- and appetitively-motivated paradigms: evidence for dopamine-reinforcer interactions

Three experiments examined the influence of the dopamine (DA) D1/D2 receptor antagonist alpha-flupenthixol on the latent inhibition (LI) effect. LI is a phenomenon which is manifest when non-reinforced pre-exposure to a stimulus retards subsequent conditioning to that stimulus, and has been proposed as an animal model of the selective attentional processes that are disrupted in acute schizophrenia. Experiment 1 extended previous findings that neuroleptics enhance the LI effect in conditioned suppression paradigms in rats to alpha-flupenthixol (0.23 mg/kg). Experiment 2 demonstrated that this enhancement of the LI effect was also seen in a parallel appetitively-motivated conditioning paradigm at the same dose. In both Experiment 1 and Experiment 2, the enhancement of the LI effect by alpha-flupenthixol appeared to be accompanied by a decrease in the impact of the reinforcer (be it appetitive or aversive). Experiment 3 investigated the possible role of the reinforcer in the effect of alpha-flupenthixol on the LI effect in the aversive, conditioned suppression paradigm by increasing the intensity of footshock in rats treated with alpha-flupenthixol. Increasing the intensity of the footshock completely abolished the enhancement of LI found following injection of alpha-flupenthixol, a result which could not be attributed to a floor effect. The results provide no support for interpretations of the influence of DA manipulations on the LI effect that draw parallels with deficits in selective attention observed in acute schizophrenia.