Conditioned taste aversion induced in rats by intracerebral or systemic administration of monoamine oxidase inhibitors

Abstract

Conditioned taste aversion (CTA) elicited by systemic or intracerebral application of the monoamine oxidase inhibitors clorgyline (C), pargyline (P) or deprenyl (D) was studied in 402 rats. Water-deprived animals were allowed 15 min access to 0.1% sodium saccharin (CS) followed 10 min later by IP or by intracerebral injection of the drug. In the latter case, the animals were anesthetized 5 min after saccharin drinking with pentobarbital and the drug was stereotaxically injected (1 microliter/min, 1-2 microliters) into the target structure. CTA was assessed in a two-choice retention test performed 2 days later. A geometric progression of three to six dosages applied to groups of rats (n = 10) was employed to establish the effective doses of the drugs which were 4, 20 and 32 mg/kg with IP and 2.5, 10 and 80 micrograms per rat with intracerebral (n. raphé magnus) injections of C, P, and D, respectively. The ratios of intracerebral to systemic dosages eliciting comparable CTA were 1:300 for C, 1:800 for P and 1:100 for D. Injections of 2.5 micrograms C and 10 micrograms P into the mesencephalic reticular formation, medial hypothalamus and cerebral cortex were ineffective, as were injections of 10 micrograms P into the nucleus of the solitary tract and cerebellum. The results indicate that CTA is elicited more efficiently by inhibition of monoamine oxidase A (selectively inhibited by C) than of monoamine oxidase B (selectively inhibited by D).

β-Carbolines found in cigarette smoke elevate intracranial self-stimulation thresholds in rats

“…The lack of ICSS threshold-lowering effects of harmane, norharmane, and harmine contrasts with findings that some clinical MAO inhibitors (e.g., selegiline) can have addiction-like effects in other assays (e.g., place conditioning) in rats or mice (Porsolt et al, 1984;Wu and Zhu, 1999), although other studies reported no abuse potential or even aversive effects of clinical MAO inhibitors as measured using i.v. self-administration in rhesus monkeys (Winger et al, 1994) or conditioned taste aversion in rats (Buresova and Bures, 1987). Our data also contrast with a report that norharmane was reinforcing in an i.v.…”

Regulation of dorsal raphe nucleus function by serotonin autoreceptors: A behavioral perspective

“…Collectively these results suggest that acute inhibition of the DRN via 5-HT 1A autoreceptors is rewarding, whereas stimulation of 5-HT 1A and 5-HT 1B heteroreceptors is aversive. This conclusion is consistent with pharmacological studies using acute administration of a serotonin-specific reuptake inhibitor or monoamine oxidase inhibitor to enhance 5-HT function, which rodents find aversive (Berendsen and Broekkamp, 1994; Buresova and Bures, 1987; Gommans et al , 1998; Prendergast et al , 1996) - but see (Olivier et al , 1999; Subhan et al , 2000). The idea of serotonin as an aversive signal has been further explored in “opponent process” theory (Boureau and Dayan, 2011; Cools et al , 2011; Daw et al , 2002).…”