Ž . Molecular Brain Research 46 1997 321–324 Short communication Opioidergic and dopaminergic gene expression in the caudate-putamen ž ) and accumbens of the mutant mouse, tottering tg r tg Andrea De Bartolomeis 1 , Vuk Koprivica, David Pickar, Jacqueline N. Crawley, Louise C. Abbott ),2 Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA Accepted 30 December 1996 Abstract Expression of preproenkephalin, dynorphin and D dopamine receptor mRNAs was examined in selected regions of the forebrain of 2 homozygous and heterozygous tottering mice, using in situ hybridization histochemistry. Homozygous tottering mice carry an autosomal recessive mutation causing them to exhibit petit mal-like epilepsy. Preproenkephalin mRNA levels were significantly higher in the lateral caudate and the core of the nucleus accumbens of homozygous tottering mice compared to wild-type controls. No differences were observed in the expression of dynorphin and D receptor mRNA distribution in brain regions examined in the mutant mice as compared 2 to wild-type controls. q 1997 Elsevier Science B.V. All rights reserved. Keywords: Enkephalin; Dynorphin; D dopamine receptor; mRNA; Epilepsy; Striatum; Hybridization histochemistry, in situ 2 Ž . The autosomal recessive mutation, tottering tg , is located on the eighth chromosome in the mouse, however, the gene carrying the tottering mutation is unknown. Ho- Ž . mozygous tottering mice tg r tg ) 3 weeks of age dis- w x Ž. play a triad of neurological disorders 18 consisting of: 1 Ž. ataxia; 2 an intermittent movement disorder similar to w x Ž. focal myoclonus 9,12 ; and 3 bilaterally symmetrical Ž . spike-wave discharges 6–7 cyclesrs which are character- ized by the presence of a fixed, staring posture and no evidence of any postictal depression, thus, closely resem- bling the absence seizures of human petit mal epilepsy. Ž . Heterozygous tottering mice tg rq have not been re- ported to exhibit any obvious seizure activity. Earlier investigations have established the presence of hyperinner- vation of adrenergic terminals in many locus coeruleus ) Ž . Corresponding author. Fax: q1 409 847-8981; E-mail: labbott@cvm.tamu.edu 1 Current address: Department of Neuroscience and Interhuman Com- munication, Section of Psychiatry, University School of Medicine, Fed- erico II, via Pansini 5, 80131 Napoli, Italy. 2 Current address: Department of Veterinary Anatomy and Public Health, College of Veterinary Medicine, Texas A&M University, College Ž Station, TX 77843-4458, USA previous address: Department of Veteri- nary Biosciences, College of Veterinary Medicine, University of Illinois . at UrbanarCampaign, Urbana, IL 61801, USA . target regions in the tg r tg brain which is believed to be correlated with the observed petit mal-like seizure behav- w x ior 14,17 . Previous studies have revealed that endogenous brain ligands for opioid receptors, such as leucine- or methion- ine-enkephalin and b-endorphin, may be involved in both w x generalized and partial seizures 7,13,23,24 . Elevated con- centrations of methionine-enkephalin have been reported w x in the striatum of tg r tg mice 19 and the present study was undertaken to expand this original study. We chose to investigate opioid gene expression for preproenkephalin and dynorphin at the transcriptional level in specific re- gions of the caudate-putamen and accumbens of homozy- gous and heterozygous tottering mice by means of in situ hybridization histochemistry. In addition, considering the demonstrated relationship between the D dopamine recep- 2 w x tor and enkephalin in the rodent striatum 1,20 , we also examined D dopamine receptor gene expression in the 2 same brain regions. Preliminary data were presented previ- wx ously in abstract form 4 . Animals and tissue processing. Breeding and experi- mental mice all were of the inbred strain, C57BLr6J, and production of homozygous and heterozygous mice fol- w x lowed previously published methods 11 . All mice were maintained in the breeding facility located at the Univer- 0169-328Xr97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S0169-328X 97 00027-2