ABSTRACT
The extracellular concentration of dopamine in the ventral striatum was measured daily by means of brain microdialysis. Chronic cocaine (10 mg/kg twice daily) altered the dopamine output compared to that in vehicle-injected rats, inducing a pronounced increase in the first 3 days followed by a clear-cut decrease. This reduction in the output of dopamine during chronic cocaine as well as during withdrawal may be neurochemical substrate for the addictive properties of cocaine.
Subject(s)
Cocaine/pharmacology , Dopamine/metabolism , Limbic System/drug effects , Substance-Related Disorders/metabolism , Animals , Limbic System/metabolism , Male , Rats , Rats, Inbred Strains , Time FactorsABSTRACT
The regulation of acetylcholine (ACh) release by the different subtypes of muscarinic (M) receptors in the hippocampus of freely-moving Fischer and Sprague-Dawley rats, was investigated. Atropine (10 mumol/kg i.p.) induced a pronounced increase of ACh release (+400% over basal values) in the hippocampus of young rats (3 months) while the effect was drastically reduced (+100% over basal values) in old rats (24 months). The preferential M2 antagonist AF-DX 116 (50 mumol/kg i.p.) showed similar effects in young and old rats being, furthermore, 10 times less potent than atropine. The preferential M1 antagonist pirenzepine (50 mumol/kg i.p.) was even less potent than AF-DX 116 in enhancing ACh release in young rats, while the effect was more pronounced in the old ones. Therefore, the effect of the preferential M3 antagonist 4-DAMP was studied. 4-DAMP 10(-6) M, dissolved in the Ringer solution perfusing the hippocampus, induced an enhancement of ACh release (+200% and +70% over basal values, in young and old rats, respectively) which was comparable to that obtained after atropine at the same concentration. AF-DX 116 and pirenzepine, on the other hand, were by far less potent. Six months' pretreatment with acetyl-l-carnitine (ALCAR) reduced the significant differences between young and old rats in the release response after M1 and M3 receptor antagonists. Taken all together, these findings indicate that the regulation of ACh release, at least in the hippocampus, is mainly through the M3 receptors subtype of muscarinic receptors and that this subtype is the most involved in the aging process. Moreover, the ability of ALCAR to preserve the receptor-mediated functional ACh release response with respect to old animals suggests that ALCAR could be utilized in the amelioration of receptor functionality in the aging brain.
Subject(s)
Acetylcarnitine/pharmacology , Acetylcholine/metabolism , Hippocampus/growth & development , Aging , Analysis of Variance , Animals , Atropine/pharmacology , Hippocampus/drug effects , Hippocampus/metabolism , Male , Parasympatholytics/pharmacology , Pirenzepine/analogs & derivatives , Pirenzepine/pharmacology , Rats , Rats, Inbred F344 , Rats, Inbred Strains , Reference ValuesSubject(s)
Caudate Nucleus/metabolism , Dopamine/metabolism , Nucleus Accumbens/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Animals , Behavior, Animal/drug effects , Caudate Nucleus/drug effects , Dizocilpine Maleate/pharmacology , Male , Nucleus Accumbens/drug effects , Organophosphorus Compounds/pharmacology , Perfusion , Piperazines/pharmacology , Rats , Rats, Inbred Strains , Receptors, N-Methyl-D-Aspartate/drug effects , Stereotyped Behavior/drug effectsABSTRACT
Systemic administration of the 5-HT3 receptor antagonist ICS 205-930, but not of the benzodiazepine diazepam, was able to prevent the stimulation of dopamine release in the nucleus accumbens and prefrontal cortex induced by restraint stress. These findings suggest that stress is not simply co-extensive with anxiety and that 5-HT3 receptors could regulate the dopaminergic response to stress.
