Thyrotropin releasing hormone and rotational behaviour in rats

Thyrotropin releasing hormone and rotational behaviour in rats

273 PERIPHERAL NEURONAL SYSTEMSSHOWMARKEDINCREASES IN VIP/PHI AND CCK CONTENT FOLLOWING INJURY P ANAND, S J GIBSON*, G P McGREGOR, M A BLANK, Y YIANG...

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PERIPHERAL NEURONAL SYSTEMSSHOWMARKEDINCREASES IN VIP/PHI AND CCK CONTENT FOLLOWING INJURY P ANAND, S J GIBSON*, G P McGREGOR, M A BLANK, Y YIANGOU, A J BACARESEHAMILTON, J M POLAK* and S R BLOOM, Department of Medicine and Histochemistry* Hammersmith Hospital, Du Cane Road, London, WI20HS. We have discovered a group of neurons in the s c i a t i c nerve of the rat that show a remarkable early and persistent increase in VIP and PHI levels (+ 1000% to + 2000%) and CCK content following peripheral section: in contrast, the substance P level decreases (-50%), as may be expected from previous results. Our previous studies show that peripheral nerve section in rats, and inoculation of Mycobacterium leprae into hind footpads of mice, increased VIP/PHI levels in i p s i l a t e r a l lumbar dorsal cord, whereas dorsal rhizotomy in rats and cats decreased them. I t was thus considered more l i k e l y that the cell bodies of these VIP/PHI peripheral neurons lay in the dorsal root ganglia than in the sympathetic ganglia. However, capsaicin application to the nerve before section failed to abolish the rise of VIP/PHI. Local capsaicin treatment alone also increased VIP/PHI levels, while decreasing substance P levels. Our working hypothesis is that whatever t h e i r o r i g i n , these VIP/PHI and CCK containing neurons play a role in the pathophysiological changes following injury and disease, possibly related to local vasodilatation. They may be diagnostic markers of peripheral nerve i n j u r y ; more importantly, they may provide a rationale for, and a predictor of, the effect of sympathectomy in pain syndromes, including causalgia.

THYROTROPIN RELEASING HORMONE AND ROTATIONAL BEHAVIOUR IN RATS J.S. ANDREWS and A. SAHGAL, MRC N e u r o e n d o c r i n o l o g y unit, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, NE4 6BE. Cohn et al (1975) reported that intraventricular administration of thyrotropin releasing hormone (TRH) enhanced r o t a t i o n in u n l e s i o n e d a n i m a l s p r e t r e a t e d w i t h a p o m o r p h i n e , although the evidence for rotation in response to TRH alone is controversial. We explored the effects of intraventricular administration of TRH and a metabolite, histidyl-proline diketopiperazine (DKP) on rotational behaviour in rats. Unilateral lesions of the substantia nigra were made by infusion of 15 ~g of 6-hydroxydopamine in 3 ~i of s a l i n e ; g u i d e c a n n u l a w e r e a l s o i m p l a n t e d into the l a t e r a l ventricle. Lesions and placements were subsequently verified. Rats w e r e d i v i d e d i n t o 3 g r o u p s (saline, TRH, DKP), and t e s t e d for r o t a t i o n in r e s p o n s e to a m p h e t a m i n e , a n d c o - a d m i n i s t r a t i o n of peptide/amphetamine; a similar procedure was carried out using apomorphine in the same animals. The results show that TRH and DKP can modulate drug induced r o t a t i o n in rats, e v e n t h o u g h c i r c l i n g in r e s p o n s e to e i t h e r peptide alone is minimal. DKP had a greater effect on amphetamine rotation than TRH or saline, but TRH had a more m a r k e d effect on apomorphine circling. Cohn et al 1975 Brain Res. 96, 134-137.