Psychopharmacology (Berl). 1990;102(2):183-90.
Self-administration in baboons and the discriminative stimulus effects in rats of bupropion, nomifensine, diclofensine and imipramine.

Lamb RJ, Griffiths RR.

Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD 21225.

The behavioral effects of the antidepressants nomifensine, diclofensine, bupropion, and imipramine were examined using a cocaine substitution drug self-administration procedure in baboons and a cocaine drug discrimination procedure in rats. Intravenous self-administration of the antidepressants was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a fixed-ratio 80-response or 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time-out allowing a maximum of eight injections per day. The antidepressants or their vehicles were substituted for cocaine for a period of 15 days, followed by a return to the cocaine baseline. Nomifensine, diclofensine and bupropion all maintained self-administration behavior at levels above those maintained by their respective vehicles. Some doses of nomifensine, diclofensine, and bupropion maintained levels of behavior similar to those maintained under baseline cocaine conditions. High doses of imipramine maintained levels of behavior above those maintained by its vehicle, but the amount of behavior maintained under these conditions was extremely small. In a second experiment rats were trained to discriminate 32 mumol/kg cocaine (IP 10 min presession) from no drug in a two-lever food reinforced drug discrimination procedure in which responding on one lever was reinforced following ten consecutive responses when the session was preceded by cocaine administration, while responding on the other lever was similarly reinforced in the absence of cocaine pretreatment. Cocaine, nomifensine, diclofensine, and




Pharmacol Biochem Behav. 1990 Oct;37(2):247-52.
Effects on opioid-induced rate reductions by doxepin and bupropion.

Macenski MJ, Cleary J, Thompson T.

University of Minnesota, Department of Psychology, Minneapolis 55455.

Twelve pigeons key-pecked under a multiple variable interval 15-second, variable interval 150-second schedule of food reinforcement. Effects of two opioid drugs, buprenorphine and methadone, were determined alone and in combination with chronic daily administration of the antidepressants doxepin or bupropion. Methadone initially produced dose-dependent key-pecking rate reductions when administered acutely, prior to the session, while buprenorphine produced key-pecking rates that reached a plateau at 50-80% of baseline rate and were not reduced further by higher doses. Neither doxepin nor bupropion, given alone, had lasting effects on key-pecking rates. Chronic daily doxepin administration significantly attenuated methadone-induced response rate reductions. Bupropion reduced the effect of the highest methadone dose, but this effect was mitigated by the development of opioid tolerance. Unlike bupropion, doxepin interfered with the development of opioid tolerance. Neither antidepressant systematically altered effects of buprenorphine on key-pecking.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2127853&dopt=Abstract Bupropion Wellbutrin




Neuropsychopharmacology. 1989 Dec;2(4):273-9.
Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis.

Nomikos GG, Damsma G, Wenkstern D, Fibiger HC.

Department of Psychiatry, University of British Columbia, Vancouver, Canada.

This study examined the acute effects of the novel antidepressant drug, bupropion, on extracellular concentrations of dopamine (DA), its metabolites, and the serotonin metabolite 5-HIAA in the striatum and nucleus accumbens using on-line microdialysis in freely moving rats. Bupropion HCl (10, 25, and 100 mg/kg intraperitoneally) increased extracellular striatal DA in a dose- and time-dependent manner; 1 mg/kg did not affect extracellular DA. The maximal response occurred within the first 20 minutes (+76%, +164%, and +443% for each dose, respectively) followed by a gradual decrease to a stable but elevated level for the next 2 hours. This neurochemical response was strongly associated with bupropion-induced stereotyped behavior during the first hour but not during the subsequent 2 hours. Bupropion decreased DOPAC concentrations, increased 5-HIAA, and had variable effects on homovanillic acid (HVA) (decreases with 10 mg/kg and increases with 25 and 100 mg/kg). The increase in extracellular DA after bupropion (25 mg/kg) was blocked by tetrodotoxin and was therefore action-potential-dependent. Bupropion produced similar neurochemical responses in the striatum and the nucleus accumbens. These results suggest that increases in DA transmission contribute to the behavioral effects of bupropion and are consistent with a role for DA in the antidepressant effects of this drug. The partial dissociation between DA release and stereotyped behavior suggests that the relationship between neurotransmitter release and behavior may be complex.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2482026&dopt=Abstract Bupropion Wellbutrin




Biopharm Drug Dispos. 1989 Jan-Feb;10(1):35-41.
Effect of bupropion on cimetidine and ranitidine absorption in rats.

Tanira MO, Kaka JS, al-Khamis KI.

Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Cimetidine and ranitidine absorption were studied in rats, alone or in combination with concurrent but separate bupropion oral administration. Blood samples were collected before and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.5, and 6.0 h after dosing. In ranitidine-treated rats, an extra blood sample at 8 h was collected. Assays of cimetidine and ranitidine were carried out using a HPLC method. Mean cimetidine plasma concentrations on concurrent bupropion administration at 0.25 and 0.5 h were approximately 2 and 1.5 times compared to the control. Similarly, mean ranitidine plasma concentrations with bupropion combination at 0.25 and 0.5 h were significantly different and approximately 2 and 3 times higher. Time of maximum concentration for cimetidine and ranitidine on combination were reduced to almost half of the control value. However, only the time of maximum concentration for cimetidine showed statistically significant difference. No significant differences were observed between AUCs, maximum concentrations, and half-lives of cimetidine and ranitidine compared to their respective controls. The results suggest that concurrent bupropion administration may affect the rate but not the extent of absorption of cimetidine and ranitidine.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2493822&dopt=Abstract Bupropion Wellbutrin




Psychopharmacology (Berl). 1992;107(2-3):303-9.
A comparison of the effects of sibutramine hydrochloride, bupropion and methamphetamine on dopaminergic function: evidence that dopamine is not a pharmacological target for sibutramine.

Heal DJ, Frankland AT, Gosden J, Hutchins LJ, Prow MR, Luscombe GP, Buckett WR.

Boots Pharmaceuticals Research Department, Nottingham, UK.

Sibutramine hydrochloride, a novel monoamine reuptake inhibitor antidepressant, has been studied to determine whether it alters dopaminergic function in the brain. Its effects have been compared with bupropion, a dopamine reuptake inhibitor, and methamphetamine, a dopamine reuptake inhibitor and releasing agent. Sibutramine (0.1-3 mg/kg PO) and methamphetamine (0.3-30 mg/kg PO) both prevented reserpine (0.75 mg/kg IV) ptosis in rats with ED50 values of 0.6 mg/kg and 4.2 mg/kg, respectively. Bupropion (10-100 mg/kg PO) was ineffective against reserpine ptosis. The efflux of [3H]-dopamine from preloaded rat striatal slices was not altered by 10(-7)-10(-5) M concentrations of sibutramine, BTS 54,354, BTS 54,505 (secondary and primary amine metabolites, respectively) or bupropion. In contrast, methamphetamine (10(-8)-10(-4) M) caused a significant concentration-dependent increase in [3H]-dopamine release. Sibutramine (3 mg/kg IP or 6 mg/kg PO) and bupropion (10 mg/kg IP or 30 mg/kg PO) did not alter 3-methoxytyramine (3-MT) levels in rat striatum. Striatal 3-MT concentrations were, however, dose-dependently increased by methamphetamine (0.3-10 mg/kg IP or 0.42-4.2 mg/kg PO). Sibutramine (6 mg/kg PO) did not induce circling in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic neuronal tract. Bupropion (10-100 mg/kg PO) did not induce circling at the lowest dose, but caused increasing ipsilateral rotation at higher doses. Methamphetamine (0.42 or 4.2 mg/kg PO) induced ipsilateral circling with marked effects at the higher dose.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1615130&dopt=Abstract Bupropion Wellbutrin




Pharmacopsychiatry. 1989 Nov;22(6):263-5.
Lack of effect of the antidepressant compound bupropion on pineal indoleamines.

McIntyre IM, Oxenkrug GF.

Department of Psychiatry, University of Melbourne & Austin Hospital, Heidelberg, Australia.

The effects of the antidepressant compound bupropion were studied on rat pineal indoleamines. A pharmacologically relevant dose of bupropion either acutely (20 mg/kg) or chronically (20 mg/kg/day for 12 days) had no significant effect on pineal melatonin synthesis or other pineal indoleamine concentrations. The significance of this finding is discussed in relation to the lack of effect of bupropion on beta-adrenergic receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2515551&dopt=Abstract Bupropion Wellbutrin