ABSTRACT
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 10â¯ng OT. In different group of animals 4⯵g D2 DA receptor antagonist was applied. Other animals received D2 DA receptor antagonist 15â¯min before 10â¯ng OT treatment or vehicle solution into the CeA. Rats receiving 10â¯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 10â¯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.
Subject(s)
Anti-Anxiety Agents/pharmacology , Oxytocin/pharmacology , Receptors, Dopamine D2/physiology , Spatial Behavior/drug effects , Amygdala/drug effects , Amygdala/metabolism , Animals , Anxiety/drug therapy , Behavior, Animal/drug effects , Conditioning, Classical/drug effects , Dopamine D2 Receptor Antagonists/pharmacology , Fear/drug effects , Freezing Reaction, Cataleptic/drug effects , Male , Maze Learning/drug effects , Rats , Rats, Wistar , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/metabolism , Receptors, Oxytocin/metabolism , Receptors, Oxytocin/physiology , Reinforcement, Psychology , Reward , Sulpiride/pharmacologyABSTRACT
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 100â¯ng NT or 2⯵g D1 dopamine receptor antagonist alone, or D1 dopamine antagonist 15â¯min before 100â¯ng NT treatment or vehicle solution into the CeA. Other animals received 4⯵g D2 dopamine receptor antagonist Sulpiride alone, or administration of D2 dopamine receptor antagonist 15â¯min before 100â¯ng NT treatment or vehicle solution into the CeA. Rats that received 100â¯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.
Subject(s)
Central Amygdaloid Nucleus/metabolism , Conditioning, Classical/physiology , Dopamine/metabolism , Neurotensin/metabolism , Spatial Behavior/physiology , Animals , Benzazepines/pharmacology , Central Amygdaloid Nucleus/drug effects , Conditioning, Classical/drug effects , Male , Microinjections , Neurotensin/administration & dosage , Neurotransmitter Agents/pharmacology , Rats, Wistar , Receptors, Dopamine D1/antagonists & inhibitors , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/metabolism , Spatial Behavior/drug effects , Sulpiride/pharmacologyABSTRACT
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.
