Effects of serotonin type 3 receptor activity on receptive and proceptive behaviours in female rats

The n e u r o t r a n s m i t t e r s e r o t o n i n ( 5-HT) i n f l u e n c e s many c e n t r a l l y m e d i a t e d behaviours. In female r a t s , 5-HT a f f e c t s the e x p r e s s i o n of l o r d o s i s , a b e h a v i o u r a l index of sexual r e c e p t i v i t y . C o n f l i c t i n g e m p i r i c a l evidence r e g a r d i n g the r o l e of 5-HT, with r e s p e c t t o l o r d o s i s , and i d e n t i f i c a t i o n of subtypes of c e n t r a l 5-HT r e c e p t o r s l e d to f o r m u l a t i o n of the h y p o t h e s i s t h a t 5-HT p l a y s a dual r o l e with r e s p e c t to female sexual behaviour. Evidence suggests t h a t 5-HT 1 A r e c e p t o r s i n h i b i t , while 5-HT 2 r e c e p t o r s f a c i l i t a t e l o r d o s i s . The r e c e n t l y i d e n t i f i e d c e n t r a l 5-HT 3 r e c e p t o r a f f e c t s the r e l e a s e of n e u r o t r a n s m i t t e r s such as dopamine, n o r e p i n e p h r i n e and a c e t y l c h o l i n e ; modulates the e f f e c t s of o p i a t e s , amphetamine and n i c o t i n e ; and i n f l u e n c e s anxiety, l e a r n i n g , n o c i c e p t i o n , nausea and v o m i t i n g . I t remains to be determined whether 5-HT 3 r e c e p t o r s a l s o i n f l u e n c e r e p r o d u c t i v e a c t i v i t y . In female r a t s s exual a c t i v i t y i s comprised of two types of behaviours: r e c e p t i v e ( l o r d o s i s ) and p r o c e p t i v e (ear w i g g l i n g , hopping and d a r t i n g ) . In the c u r r e n t l i t e r a t u r e , l o r d o s i s stands as the primary measure; p r o c e p t i v e behaviours are seldom r e p o r t e d . The purpose of t h i s t h e s i s i s to f u r t h e r c h a r a c t e r i z e the 5 H T 3 r e c e p t o r with r e s p e c t to female r e p r o d u c t i v e a c t i v i t y and to i n c r e a s e the understanding of neurochemical f a c t o r s which i n f l u e n c e r e c e p t i v e and p r o c e p t i v e behaviours i n female r a t s . The c u r r e n t s e r i e s of experiments i n v e s t i g a t e d the e f f e c t s of 5 HT3 a g o n i s t s and a n t a g o n i s t s , a d m i n i s t e r e d alone and i n c o n j u n c t i o n with morphine and apomorphine, on sexual behaviours i n o v a r i e c t o m i z e d , s t e r o i d p r i m e d female r a t s . The 5 H T 3 a n t a g o n i s t s MDL 72222, ondansetron and ICS 205930 f a i l e d t o a f f e c t r e c e p t i v e or p r o c e p t i v e behaviours, although a t r e n d towards a f a c i l i t a t o r y e f f e c t was ev i d e n t i n the case of ondansetron. S i m i l a r l y , the 5-HT3 a g o n i s t s 1p h e n y l b i g u a n i d e and 2m e t h y l s e r o t o n i n , a d m i n i s t e r e d i n t r a c e r e b r o v e n t r i c u l a r l y , d i d not s i g n i f i c a n t l y i n f l u e n c e female c o p u l a t o r y behaviours. While low doses of morphine s i g n i f i c a n t l y i n h i b i t e d sexual a c t i v i t y , t h i s i n h i b i t i o n was not att e n u a t e d by any of the 5-HT3 a n t a g o n i s t s . Likewise, apomorphine p r o f o u n d l y i n h i b i t e d both r e c e p t i v e and p r o c e p t i v e behaviours, but these e f f e c t s were not antagonized by ICS 205930. Although these data do not support the i d e a t h a t 5-HT3 r e c e p t o r s are i n f l u e n t i a l i n the modulation of female r e p r o d u c t i v e b e h a v i o u r s , c o n s i d e r a t i o n of v a r i o u s p h a r m a c o l o g i c a l and methodological f a c t o r s c a u t i o n a g a i n s t a premature c o n c l u s i o n i n t h i s regard.