S UMMA RY OF WORK ' Drugs serve as positive reinforcers to maintain and str ength en behavior leading to thei r ad m inistration and a I n s . m can control beh vior through their ability to function as discriminative sti muli many situations , d g of abuse function throug h pha rmacological and behavioral mechanisms to persistently sustai n long seq uences k d m - of d ru g see ing behavior that are very resistant to extinction . These long seq uences of g seeking behavior can be analyzed using schedu le-controlled performances i n the same way as opera nt behavior v k U - maintained by oth er e ents such as food or shoc . sing a variety of intravenous self adm inistration i v proced ures in rats and pr mates , ongoing experiments are being conducted to e aluate behavi or maintained by d rugs and the a bility of pharmacological treatments , antagonist adm in istration or the development of dependence) and/or behavio ral manipulations to modify d rug self-administration behavior and/or food - . will n rv mai ntained behavior These stud ies compare respond ing maintained u der fixed rati o , fixed i nte al and l - i comp ex second order schedules , by var ous drugs includ ing cocaine , nicotin e and other psychomotor seda tive/a nxiol tics -9 stimu lants , benzod iazepi nes and other y , morphine and other opioids and delta THC (the t . F ac ive i ngredient of marijuana) or example , since serotonergic mechanisms appear to u nd erli e l psychomotor sti mu ant action , recent stud ies evaluated the effects of sertral ine , a selective serotonergic k f i upta e in hi bitor that is effective as a n a ntidepressant , on th e reinforcing ef ects of v . nicoti ne in sq u i rrel . I n v monkeys addition to differences in the pharmacological efficacy of d rugs to control or modify beha ior, it is clea r that behavioral and environmental factors play an important role i n the contro l that even h ig h ly - efficacious d r ugs exert on behavior. The focus of exper i ments in the rhesus self admi n istration la b are to study the pharm acolog ical , behaviora l , and environmental varia bles involved in initiating and maintaini ng - - dmg self adm inistrati on . Recent studies assessed rates of acq uisition of cocaine self i njection in rh esus mon keys found a relationship with behavioral history , but not activity level . Additional studies a re eval uating the effects of serotonerg ic antagonists on delta-amphetam ine self- injection and noradrenerg ic antagonists “ rs - I . n w and uptake i n hi bito on cocai ne self injection another study , e are evaluating the reinforci ng efficacy of I- t I - the stereoisomers of deprenyl (selegil in e) in comparison to me hamphetamine and its stereoisomer, as well - as eval uating the a bility of deprenyl pretreatment to alter self adm inistration of coca ine , metham phetam ine or beta -phenylethylamine v PHS 6040 (R e . PU BLI CATIONS - S Y S . B v m l Gold ber g R , asar eha ioral phar acology of selegil in e ( deprenyl) and its metabolites and i nt eractions - B B . with ph enylethylam i ne , P rogress in rain Research ; in press C linica l - S Youd im M B . l Gold berg R , H and preclin ical experience with deprenyl (selegi lin e) with regard to a buse P 1 994 l iability , C li nical ha rm acology and Therapeutics ; in press . - - W Y S N SS S . I v i l inger G , asa r , eg us , Goldberg R ntra enous self admin istration studies w th deprenyl (selegiline) k P 1 994 in mon eys , Cl in ical harmacology and Th erapeutics ; i n press . - - Y S Y B J . A k I r asar , ergman mphetami ne li e effect of deprenyl in d ug discrim ination studies , Cl i nical P c 1 994 ha rm acology and Therapeuti s ; in press . S u A A NA G ri . B m a e ca m il I S b . anner d C , tor , ffiths RR ehavioral phar acology of i n ba boons n : tephens DN ed . A l B - a b : Ps cho h a rrn a col o S ri B S nxio ytic c r olines from molecular biology to the clinic . y p gy e es I I . erl in : pri nger - l 20 . Ver ag , M G K E S M K BJ P KL S u A S ilver ma n K G umford , vans , , am inski , reston , anner d C , , , riffiths RR . Discr i m i native t f Ps ch o h a rrn a colo - stimu lus a nd su bjec ive effects of theobrom ine and caf eine i n hu mans , y p gy 8 . B J i - S A K k G . M H 1 annerud C , a m ins i , r ffiths RR aintenance of antagon ists self i njection i n baboons , Ex erimenta l Ps cho h a r rn a col o 1 99 p and Cli nical y p gy 4; in press . B J i - S A K G . S annerud C , ami nski , r ffiths RR elf injection of phenethyl a mine designer d ru gs i n ba boons B P m 1 994 ehavioral har acology ; in press . SUMMARY O F WORK Commercia l assays fort he detection of drugs of a buse in urine change periodically and must be reevaluated for perform ance . Stud ies are desig ned to test the validity of new assays with clin ica l specim ens obtai ned from d rug users under controlled conditions . I Healthy male volunteers with a history of chemica l su bstance a buse participate in these studies . nform ed I B consent is obtained and all procedures are approved by the hospital nstitutional Review oard . Comm ercial assays for detection of d ru gs of a buse in urine are tested for validity with speci mens col lected und er A controlled dosing conditions var iety of drugs of a buse were studied at various dose l evels . Th e resu lts of toGC/ the assays were com pared MS analysis . These studies test th e validity of commercial assays on clinical samples instead of spiked sam ples a nd provide uniq ue and valua ble information to the mil itary and industry concern ing their ti me course of detection , specificity and accuracy . PU BLI CAT I O NS M u O . k L J . F i U S . P M F E . J . Cone , , Dic erson , aul , and itchell , orens c Dr g Testing or piates V rine Testing - F r om M i A W O . A . 1 7 : 1 56 1 64 or H e , orph ne nd Codein e ith Commercial piate l mm unoassays J nal Toxicol , , 1 993 . - J k M . H A . E . O S J L . C . rw W D . EZ A . M : en ins , ills , , Da in , uestis , and Con e J Validity Testing f Th e creen 1 7 : - 292 298 1 993 . J . Canna binoid Test . Anal . Toxicol , , r S . L . W R . Fr a n ke nfie ld E . J . S . I Joseph , T , Dicke son , , ill is , , , D Cone , and m ith D R nterference by - N i A i infla mm a tor Dm s M I T A A . A . I n P onstero dal nt y g in E T and Dx ssays for Drugs of buse J na l Toxicol . ress 1 994 . D . t . J . M . c J rw W . M A M J . E . J . a cu/PI N CH enkins , A . , Da in , , H ues is , , Cone , and itchell , Valid ity Testing of the 1 994 T J A . I P THC est . nal Toxicol , n ress , . SUMMARY OF WORK The behavioral pha r macologica l profil e of a drug in a pertinent species is necessary to evaluate quantitatively how the d rug fu nctions as a reinforcer or a pun isher as well as to establish its sti m ul us effects . Sched ules of food presentation with both fixed - interval and fixed- ratio com ponents have been used most frequently i n th is type of study since they generate a wide range of rates and patterns of respond ing withi n a - a ls . session a nd provide sta ble , long term baselines for chron ic studies in individ ual a nim Th e present project involves the assessm ent of both the acute and chronic effects of a variety of drugs on schedu le-controll ed behavior . We have recently shown that the enhanced sensitivity observed to the behaviora l effects of the GA BA er ic opioid antagonist naltrexone is influenced by g processes , and in pa rticular by an action at the ABA . F rt G associated chl oride channel u her , this sensitivity may be associated with cha nges i n both m u and delta opioid recepto r s . Genetic factors are known to influence the behavioral effects of a nu m ber of different u n dr gs , and studies of the i nteractions betwee environmental and genetic components th at potentially affect l the deve opment of behaviora l tolerance and sensitivity are being initiated .