+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Acute and chronic amphetamine treatments differently regulate neuropeptide messenger RNA levels and Fos immunoreactivity in rat striatal neurons



Acute and chronic amphetamine treatments differently regulate neuropeptide messenger RNA levels and Fos immunoreactivity in rat striatal neurons



Neuroscience 65(4): 1041-1050



Repeated administration of amphetamine results in the well known phenomenon of reverse tolerance or sensitization. However, little is known about cellular and molecular mechanisms underlying acute versus chronic response to amphetamine. In this paper, we investigated the effects of acute (1.5 or 5 mg/kg) and chronic (5 mg/kg/day for 14 days) amphetamine treatment on locomotor activity, stereotypy, Fos immunoreactivity and messenger RNA levels of molecules implicated in dopamine transmission in the rat striatum and substantia nigra. In agreement with other studies, acute amphetamine induced a dose dependent increase in locomotor activity and stereotypy. Also, a comparison between the behavior observed after the first injection and the last injection of amphetamine in chronically treated rats showed sensitization as demonstrated by a higher rating of stereotypy. We have found that acute and chronic amphetamine treatments differently modulate the activity of several output neurons. A double labeling procedure with Fos immunohistochemistry coupled with in situ hybridization demonstrated that acute amphetamine treatment induces Fos immunoreactivity predominantly in striatal neurons expressing substance P messenger RNA (77.07 +/- 1.42%). Only 32.6 +/- 2.07% of Fos immunoreactive neurons expressed preproenkephalin A messenger RNA. In chronic amphetamine treated rats, 56.21 +/- 1.32% of the Fos immunoreactive neurons expressed substance P messenger RNA while 52.12 +/- 1.84% expressed preproenkephalin A messenger RNA. Statistical analysis revealed that this difference is mainly due to a decrease in the density of substance P immunoreactive neurons in chronically treated rats in comparison to acute. Amphetamine treatments induced Fos immunoreactivity in the substantia nigra in non-dopamine neurons. As measured by quantitative in situ hybridization, acute amphetamine induced an increase in substance P, preproenkephalin A and dynorphin messenger RNA levels (+23 +/- 0.05%, +45 +/- 0.07% and +24 +/- 0.05%, respectively). No difference in these increases was observed in relation with the dose injected (1.5 or 5 mg/kg). Chronic amphetamine treatment enhanced only substance P and dynorphin messenger RNA levels (+23 +/- 0.04% and +42 +/- 0.04%, respectively). Neither acute nor chronic amphetamine treatment had any effects on D1 or D2 dopamine receptor messenger RNA levels. Our main conclusions are: (1) in acutely treated rats Fos is essentially expressed by substance P neurons; (2) in chronically treated rats, Fos immunoreactivity is expressed by the two efferent striatal populations (i.e. preproenkephalin A and substance P neurons) and the number of Fos immunoreactive neurons is reduced as compared with acute; (3) neuropeptide messenger RNA levels, but not dopamine receptor messenger RNAs, are affected in the response to acute or chronic treatment with amphetamine.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 008104946

Download citation: RISBibTeXText

PMID: 7617160

DOI: 10.1016/0306-4522(94)00537-f


Related references

Striatal metabotropic glutamate receptors regulate acute amphetamine-stimulated neuropeptide gene expression in the rat striatum. Society for Neuroscience Abstracts 22(1-3): 809, 1996

Acute and chronic amphetamine treatments modulate striatal dopamine receptor binding sites. Brain Research 161(1): 173-178, 1979

Muscarinic receptors regulate striatal neuropeptide gene expression in normal and amphetamine-treated rats. Neuroscience 75(1): 43-56, 1996

D-1 dopamine receptor agonist-induced fos-like immunoreactivity occurs in basal forebrain and mesopontine tegmentum cholinergic neurons and striatal neurons immunoreactive for neuropeptide Y. Neuroscience 59(2): 375-387, 1994

Pharmacological characterization of dopaminergic influence on expression of neuropeptide Y immunoreactivity by rat striatal neurons. Neuroscience 26(3): 809-817, 1988

Effect of withdrawal duration after chronic amphetamine on striatal acetylcholine response to acute amphetamine challenge. Society for Neuroscience Abstracts 22(1-3): 360, 1996

Changes in neuropeptide immunoreactivity in cultured adult mouse sensory neurons following methylmercury chloride treatments. Neuroscience Letters 246(1): 13-16, Il 17, 1998

Striatal homovanillic acid levels in rats after combined treatments with amphetamine and neuroleptics. European Journal of Pharmacology 17(2): 297-300, 1972

Effects of acute and subchronic d-amphetamine on ventral striatal concentrations of neurotensin and neuropeptide Y in rats treated with antipsychotic drugs. European Neuropsychopharmacology 16(8): 592-600, 2006

Susceptibility of striatal neurons to excitotoxic injury correlates with basal levels of Bcl-2 and the induction of P53 and c-Myc immunoreactivity. Neurobiology of Disease 20(2): 562-573, 2005

The relationship between oral dyskinesias produced by long-term haloperidol treatment, the density of striatal preproenkephalin messenger RNA and enkephalin peptide, and the number of striatal neurons expressing preproenkephalin messenger RNA in rats. Neuroscience 88(1): 27-35, 1999

Characterization of striatal neurons expressing high levels of glutamic acid decarboxylase messenger RNA. Brain Research 492(1-2): 237-244, 1989

Chronic phorbol ester treatment may regulate anf and bnp mrna levels differently. Hypertension (Dallas) 20(3): 444, 1992

Effects of peripheral nerve injuries and tissue inflammation on the levels of neuropeptide Y-like immunoreactivity in rat primary afferent neurons. Brain Research 598(1-2): 349-352, 1992

Neuropeptide Y mRNA and immunoreactivity in hypothalamic neuroendocrine neurons: effects of adrenalectomy and chronic osmotic stimulation. Journal of Neuroscience 13(3): 1138-1147, 1993