Erika Kertes

The role of neurotensin in passive avoidance learning in the rat central nucleus of amygdala

Tridecapeptide neurotensin (NT) acts as a neurotransmitter and/or neuromodulator and plays a role in learning and reinforcement. The central nucleus of amygdala (CeA), which is relatively rich in NT and neurotensin-1 receptors (NTS1), participates in the regulation of memory and learning mechanisms. The aim of this study was to examine the possible effect of NT and NTS1 antagonist (ANT) on passive avoidance learning after their microinjection into the CeA of male wistar rats. NT significantly increased the latency time. Effect of NT was blocked by ANT pretreatment. ANT in itself had no effect. Our results show that in the rat CeA NT facilitates passive avoidance learning via NTS1.

Effects of neurotensin in amygdaloid spatial learning mechanisms

Neurotensin (NT) acts as a neurotransmitter and/or neuromodulator and plays a role in learning and reward related processes. The central nucleus of amygdala (CeA) participates in the regulation of memory and learning mechanisms. In Morris water maze test, rats were microinjected with NT or neurotensin receptor-1 (NTS1) antagonist SR 48692 (ANT). NT significantly reduced the escape latency. Effect of NT was blocked by ANT pretreatment. Our results show that in the rat CeA NT facilitates spatial learning. We clarified that NTS1s are involved in this action.

Positive reinforcing effects of substance P in the rat central nucleus of amygdala

Substance P (SP) can have positive reinforcing or aversive properties, depending on the dose used and the site of action in the brain. Experimental findings suggest that the amygdala is involved in reward-related processes. The presence of SP-immunoreactive fibers and cell bodies has been shown in the central nucleus (ACE) and neurokinin (NK)-1 and NK-3 receptors also could be found there. The rewarding or aversive effects of SP in the ACE were tested in conditioned place preference paradigm. 10 ng SP microinjections had positive reinforcing properties, while 100 ng SP had no effect. Prior treatment with NK-1 receptor antagonist could block the rewarding effects of SP, while the antagonist on its own did not influence place preference. Our results show that SP and NK-1 receptors play important roles in amygdaloid rewarding-reinforcing mechanisms.

The role of neurotensin in positive reinforcement in the rat central nucleus of amygdala.

In the central nervous system neurotensin (NT) acts as a neurotransmitter and neuromodulator. It was shown that NT has positive reinforcing effects after its direct microinjection into the ventral tegmental area. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, regulation of feeding, anxiety and emotional behavior. By means of immunohistochemical and radioimmune methods it was shown that the amygdaloid body is relatively rich in NT immunoreactive elements and NT receptors. The aim of our study was to examine the possible effects of NT on reinforcement and anxiety in the CeA. In conditioned place preference test male Wistar rats were microinjected bilaterally with 100 or 250 ng NT in volume of 0.4 microl or 35 ng neurotensin receptor 1 (NTS1) antagonist SR 48692 alone, or NTS1 antagonist 15 min before 100 ng NT treatment. Hundred or 250 ng NT significantly increased the time rats spent in the treatment quadrant. Prior treatment with the non-peptide NTS1 antagonist blocked the effects of NT. Antagonist itself did not influence the reinforcing effect. In elevated plus maze test we did not find differences among the groups as far as the anxiety index (time spent on the open arms) was concerned. Our results suggest that in the rat ACE NT has positive reinforcing effects. We clarified that NTS1s are involved in this action. It was also shown that NT does not influence anxiety behavior.

Positive reinforcing effect of oxytocin microinjection in the rat central nucleus of amygdala

Neuropeptide oxytocin (OT) receives increasing attention since, it plays a role in various behaviors including anxiety, drug addiction, learning, social recognition, empathy, pair bonding and decreased aggression. The central nucleus of the amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. CeA was shown to be rich in OT-receptors (OTR). The aim of our study was to examine the possible effects of OT and OTR antagonist in the CeA on reinforcement using the conditioned place preference test and on anxiety using the elevated plus maze test. Male Wistar rats were microinjected bilaterally with 10 ng OT or 100 ng OT (Sigma: O6379, injected in volume of 0.4μl) or 10ng OTR antagonist (Sigma: L-2540) alone, or OTR antagonist 15 min prior 10 ng OT treatment or vehicle solution into the CeA. Rats receiving 10 ng OT spent significantly more time in the treatment quadrant during the test session, while 100 ng OT treatment produced no effect. Prior treatment with the non-peptide OTR antagonist blocked the effects of OT. The antagonist in itself did not influence the place preference. The elevated plus maze test revealed that 10 ng OT significantly increased the time spent in the open arms. OTR antagonist pre-treatment could inhibit this effect and the antagonist in itself did not affect the time spent in the open arms. Our results show that in the rat CeA OT has dose-dependent, positive reinforcing and anxiolytic effects, via OTR demonstrated by the blocking effects of selective OTR antagonist.

Substance P and neurotensin in the limbic system: Their roles in reinforcement and memory consolidation

HIGHLIGHTSSP and NT have rewarding effects in various limbic structures.SP and NT facilitate memory consolidation.These effects are mediated mainly by NK1 SP and NTS1 NT receptors.SP and NT influence synaptic plasticity via modulation of DA and ACh systems. ABSTRACT Substance P (SP) and neurotensin (NT) are neuropeptides isolated in the periphery and in the central nervous system. They are involved in various regulatory processes in the gastrointestinal tract, in the circulatory and respiratory systems, kidney and endocrine system. In addition to the peripheral effects, SP and NT act as neurotransmitters and neuromodulators in the central nervous system, regulating various behavioural actions, such as general and motor activity, pain, food and water intake, anxiety, reward/reinforcement and memory consolidation. In the limbic system SPergic and NTergic pathways, terminals and related receptors have been identified. According to several data of literature and to our recently published results, SP and NT have rewarding/reinforcing effects and facilitate memory consolidation in various limbic regions. In this report evidences are provided about the interaction of these neuropeptides with dopaminergic and acetylcholinergic systems. A hypothesis is presented that rewarding/reinforcing effects of SP and NT develop by modulating the mesencephalic dopaminergic system, while their mnemonic effects are mediated via the mesencephalic dopaminergic and the basal forebrain cholinergic systems.

Anxiolytic effect of neurotensin microinjection into the ventral pallidum

Neurotensin (NT) acts as a neurotransmitter and neuromodulator in the central nervous system. NT is involved in reward and memory processes, drug addiction and also in the regulation of anxiety. The ventral pallidum (VP) receives neurotensinergic innervation from the ventral striatopallidal pathway originating from the nucleus accumbens. Positive reinforcing effects of NT in the VP had been shown recently, however the possible effects of NT on anxiety have not been examined yet. In our present experiments, the effects of NT on anxiety were investigated in the VP. In male Wistar rats bilateral microinjections of 100 ng or 250 ng NT were delivered in the volume of 0.4 μl into the VP, and elevated plus maze (EPM) test was performed. In another groups of animals, 35 ng NT-receptor 1 (NTR1) antagonist SR 48,692 was applied by itself, or microinjected 15 min before 100 ng NT treatment. Open field test (OPF) was also conducted. The 100 ng dose of NT had anxiolytic effect, but the 250 ng NT did not influence anxiety. The antagonist pretreatment inhibited the effect of NT, while the antagonist itself had no effect. In the OPF test there was no difference among the groups. Our present results show that microinjection of NT into the VP induces anxiolytic effect, which is specific to the NTR1 receptors because it can be eliminated by a specific NTR1 antagonist. It is also substantiated that neither the NT, nor the NTR1 antagonist in the VP influences locomotor activity.

Role of ventral pallidal D2 dopamine receptors in the consolidation of spatial memory

The role of dopamine (DA) receptors in spatial memory consolidation has been demonstrated in numerous brain regions, among others in the nucleus accumbens which innervates the ventral pallidum (VP). The VP contains both D1 and D2 DA receptors. We have recently shown that the VP D1 DA receptor activation facilitates consolidation of spatial memory in Morris water maze test. In the present study, the role of VP D2 DA receptors was investigated in the same paradigm. In the first experiment, the D2 DA receptor agonist quinpirole was administered into the VP of male Wistar rats in three doses (0.1, 1.0 or 5.0μg, respectively in 0.4μl physiological saline). In the second experiment, the D2 DA receptor antagonist sulpiride was applied to elucidate whether it can antagonise the effects of quinpirole. The antagonist (4.0μg, dissolved in 0.4μl physiological saline) was microinjected into the VP either by itself or prior to 1.0μg agonist treatment. Control animals received saline in both experiments. The two higher doses (1.0 and 5.0μg) of the agonist accelerated memory consolidation relative to controls and increased the stability of the consolidated memory against extinction. Sulpiride pretreatment antagonised the effects of quinpirole. In addition, the antagonist microinjected into the VP immediately after the second conditioning trial impaired learning functions. The present data provide evidences for the important role of VP D2 DA receptors in the consolidation and stabilization of spatial memory.

Iontophoretic microlesions with kainate or 6-hydroxidopamine in ventromedial prefrontal cortex result in deficit in conditioned taste avoidance to palatable tastants

Effects of kainate or 6-hydroxidopamine (6-OHDA) lesions in the ventromedial prefrontal cortex (vmPFC) on taste-related learning and memory processes were examined. Neurotoxins were applied by iontophoretic method to minimize the extent of lesion and the side effects. Acquisition and retention of conditioned taste avoidance (CTA) was tested to different taste stimuli (0.05 M NaCl, 0.01 M saccharin, 0.01 M citrate and 0.00025 M quinine). In the first experiment, palatability index of taste solutions with these concentrations has been determined as strongly palatable (NaCl, saccharin), weakly palatable (citrate) and weakly unpalatable (quinine) taste stimuli. In two other experiments vmPFC lesions were performed before CTA (acquisition) or after CTA (retrieval). Our results showed that both kainate and 6-OHDA microlesions of vmPFC resulted in deficit of CTA acquisition (to NaCl, saccharin and citrate) and retrieval (to NaCl and saccharin). Deficits were specific to palatable tastants, particularly those that are strongly palatable, and did not occur for unpalatable stimulus. The present data provide evidence for the important role of vmPFC neurons and catecholaminergic innervation of the vmPFC in taste related learning and memory processes.

The role of intraamygdaloid neurotensin and dopamine interaction in conditioned place preference

HighlightsNeurotensin and D1 dopamine receptor antagonist or D2 dopamine receptor antagonist were microinjected into the central nucleus of amygdala.D1 dopamine receptor antagonist SCH 23390 pretreatment or D2 dopamine receptor antagonist Sulpiride pretreatment eliminate the positive reinforcing effects of NT in conditioned place preference test.D1 dopamine receptor antagonist or D2 dopamine receptor antagonist administered alone had no effect on place preference behavior. ABSTRACT Tridecapeptide Neurotensin (NT) is widely distributed in the central nervous system where it acts as a neurotransmitter and neuromodulator. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. Our previous data showed that NT microinjected into the CeA has positive reinforcing properties. We supposed that these effects might be due to modulations of the mesolimbic dopamine system. The aim of our study was to examine in the CeA the possible effects of NT and dopamine interaction on reinforcement by conditioned place preference test. Male Wistar rats were microinjected bilaterally with 100 ng NT or 2 &mgr;g D1 dopamine receptor antagonist alone, or D1 dopamine antagonist 15 min before 100 ng NT treatment or vehicle solution into the CeA. Other animals received 4 &mgr;g D2 dopamine receptor antagonist Sulpiride alone, or administration of D2 dopamine receptor antagonist 15 min before 100 ng NT treatment or vehicle solution into the CeA. Rats that received 100 ng NT spent significantly more time in the treatment quadrant during the test session. Pre‐treatment with the D1 dopamine antagonist, blocked the effects of NT. D2 dopamine receptor antagonist pretreatment could prevent the positive reinforcing effects of NT as well. Antagonists themselves did not influence the place preference. Our results show that the rewarding effect of NT can be due to the modulation of DA system, since its effects could be blocked by either D1 dopamine or D2 dopamine antagonist preteatment.