RATIONALE: Previous studies indicate that the rewarding effect of D-1 dopamine receptor stimulation in nucleus accumbens (NAc) shell is greater in food-restricted (FR) than in ad libitum fed (AL) rats. The D-1 receptor is positively coupled to adenylyl cyclase and activates protein kinase A (PKA). OBJECTIVES: The purpose of this study was to determine whether PKA is involved in the rewarding effect of D-1 receptor stimulation and, if so, whether it is involved in the enhanced response of FR rats. MATERIALS AND METHODS: Rats were stereotaxically implanted with microinjection cannulae in NAc shell and a stimulating electrode in lateral hypothalamus. The rewarding effects of SKF-82958 (1.5 or 3.0 μg, bilaterally) in the presence and absence of PKA inhibitor, Rp-cAMPS (8.9 μg), and PKA activator, Sp-cAMPS (8.9 μg), were assessed using the curve-shift method of intracranial self-stimulation (ICSS). Basal NAc levels of DARPP-32 phosphorylated on Thr34 and Thr75 were measured. RESULTS: Rp-cAMPS increased the rewarding effect of SKF-82958 in AL but not FR rats, doubling the ICSS threshold-lowering effect of the 3.0-μg dose. Sp-cAMPS decreased the rewarding effect of SKF-82958 in FR but not AL rats. Levels of phospho-DARPP-32 (Thr75), which inhibits PKA, were higher in FR than AL rats. CONCLUSIONS: Results indicate that inhibition of PKA enhances the unconditioned rewarding effect of D-1 receptor stimulation and that decreased PKA may be involved in the effect of FR on drug reward. Evidence for involvement of D-2 receptor-expressing neurons in the enhancing effect of PKA inhibition is discussed.
RATIONALE: Previous studies indicate that the rewarding effect of D-1 <span class="Chemical">dopamine receptor stimulation in nucleus accumbens (NAc) shell is greater in food-restricted (FR) than in ad libitum fed (AL) rats. The D-1 receptor is positively coupled to adenylyl cyclase and activates protein kinase A (PKA). OBJECTIVES: The purpose of this study was to determine whether PKA is involved in the rewarding effect of D-1 receptor stimulation and, if so, whether it is involved in the enhanced response of FR rats. MATERIALS AND METHODS:Rats were stereotaxically implanted with microinjection cannulae in NAc shell and a stimulating electrode in lateral hypothalamus. The rewarding effects of SKF-82958 (1.5 or 3.0 μg, bilaterally) in the presence and absence of PKA inhibitor, Rp-cAMPS (8.9 μg), and PKA activator, Sp-cAMPS (8.9 μg), were assessed using the curve-shift method of intracranial self-stimulation (ICSS). Basal NAc levels of DARPP-32 phosphorylated on Thr34 and Thr75 were measured. RESULTS: Rp-cAMPS increased the rewarding effect of SKF-82958 in AL but not FR rats, doubling the ICSS threshold-lowering effect of the 3.0-μg dose. Sp-cAMPS decreased the rewarding effect of SKF-82958 in FR but not AL rats. Levels of phospho-DARPP-32 (Thr75), which inhibits PKA, were higher in FR than AL rats. CONCLUSIONS: Results indicate that inhibition of PKA enhances the unconditioned rewarding effect of D-1 receptor stimulation and that decreased PKA may be involved in the effect of FR on drug reward. Evidence for involvement of D-2 receptor-expressing neurons in the enhancing effect of PKA inhibition is discussed.
Authors: K Fuxe; L F Agnati; K Jacobsen; J Hillion; M Canals; M Torvinen; B Tinner-Staines; W Staines; D Rosin; A Terasmaa; P Popoli; G Leo; V Vergoni; C Lluis; F Ciruela; R Franco; S Ferré Journal: Neurology Date: 2003-12-09 Impact factor: 9.910
Authors: Todor V Gerdjikov; Andrew C Giles; Shelley N Swain; Richard J Beninger Journal: Psychopharmacology (Berl) Date: 2006-10-18 Impact factor: 4.530
Authors: J A Bibb; J Chen; J R Taylor; P Svenningsson; A Nishi; G L Snyder; Z Yan; Z K Sagawa; C C Ouimet; A C Nairn; E J Nestler; P Greengard Journal: Nature Date: 2001-03-15 Impact factor: 49.962