The role of D2 dopamine receptors in oxytocin induced place preference and anxiolytic effect.

Neuropeptide oxytocin (OT) is involved in the regulation of social and non-social behaviour. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. CeA has been shown to be rich in OT receptors in rodents. Our previous findings indicated that OT in the rat CeA has a dose dependent rewarding and anxiolytic effect. The aim of our present study was to examine in the CeA the possible interaction of OT and D2 dopamine (DA) receptor antagonist Sulpiride on reinforcement in place preference test and on anxiety in elevated plus maze test. Wistar rats were microinjected bilaterally with 10 ng OT. In different group of animals 4 µg D2 DA receptor antagonist was applied. Other animals received D2 DA receptor antagonist 15 min before 10 ng OT treatment or vehicle solution into the CeA. Rats receiving 10 ng OT spent significantly longer time in the treatment quadrant during the test session in conditioned place preference test. Prior treatment with D2 DA receptor antagonist blocked the rewarding effects of OT. Antagonist in itself did not influence the time rats spent in the treatment quadrant. In elevated plus maze test, rats receiving 10 ng OT spent significantly longer time on the open arms. Prior treatment with D2 DA receptor antagonist blocked the effects of OT. Our results show that DA system plays a role in positive reinforcing and anxiolytic effects of OT because D2 DA receptor antagonist can block these actions.

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

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 µg 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 µg 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.

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

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.

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.

[Delayed effects of neurotensin microinjections into the substantia nigra on conditioned motor reactions of rats with lesions to serotoninergic neurons]. / Posledeistvie mikroin''ektsii neirotenzina v chernuiu substantsiiu mozga na uslovnye dvigatel'nye reaktsii krys s povrezhdeniem serotoninergicheskikh neironov.

Behavioral effects of neurotensin microinjections into the brain substantia nigra of rats with neurotoxic (5,7-dihydroxytryptamine) lesions of serotoninergic neurons in the dorsal raphe nucleus were studied. It was shown that neurotensin facilitated extinction of conditioned and intertrial reactions to negative (unreinforced) stimuli, but did not change the actualization of positive (with water reward) conditioned signals. Neurotensin-induced effects persisted in subsequent experiments without injections of the peptide. Neurotensin injections reduced the negative emotional states of lesioned animals in the arena during testing conditioned preference. It was concluded that the behavioral effects of neurotensin can be explained by the formation in the lesioned animals of the situational emotional state facilitating adaptive brain functions.

Effects of pretreatment with PACAP on the infarct size and functional outcome in rat permanent focal cerebral ischemia.

PACAP exerts neuroprotective effects under various neurotoxic conditions in vitro. In vivo, it reduces brain damage after global and transient focal ischemia. The present study investigated whether PACAP has neuroprotective effects when applied before the onset of permanent ischemia. Rats were given bolus injections of PACAP38 intracerebroventricularly, and then underwent permanent middle cerebral artery occlusion. The results show that 2 microg of PACAP significantly reduced the infarct size measured 12 and 24h after the onset of ischemia. No further reduction was obtained by a 7-day pretreatment. PACAP also ameliorated certain sensorimotor deficits. Our present study provides further evidence for the neuroprotective effects of PACAP, and implies that it might be a promising preventive therapeutic agent in ameliorating ischemic brain damage.