lithium-chloride and ecopipam

Conditioned saccharin avoidance (CSA) can be produced when either lithium chloride (LiCl) or a reinforcing drug, such as morphine, is administered following exposure to the taste of saccharin. In this study we investigated the involvement of dopamine (DA) transmission in the acquisition of morphine and LiCl-CSA. CSA was evaluated in a two-bottle choice paradigm with two conditioning pairings between saccharin and morphine or LiCl as unconditioned stimulus (US). Morphine hydrochloride (7.5 mg/kg s.c.) or LiCl (40 mg/kg i.p.), administered 45 and 120' respectively after saccharin-drinking session, induced strong CSA. The DA D(1) receptor antagonist, SCH 39166 (0.1 mg/kg s.c.), impaired morphine-CSA if administered 15' and, to a lesser extent, 30' but not 45' before the drug (i.e immediately after saccharin drinking). In contrast SCH 39166 reduced LiCl-CSA when administered 45' before the drug and even more so when administered 105' before LiCl i.e. immediately after saccharin drinking. Therefore SCH 39166 impaired morphine-CSA when given shortly before the drug, while it impaired LiCl-CSA when given shortly after saccharin. Raclopride, a specific antagonist of D(2) receptors, failed to affect LiCl- and morphine-CSA. These results are consistent with the idea that DA, acting on D(1) receptors, plays a differential role in morphine- and LiCl-CSA. In LiCl-CSA DA is necessary for the processing (consolidation) of the short-term memory trace of the saccharin taste to be associated with the lithium-induced aversive state, while in morphine CSA contributes to mediate the appetitive properties of the drug.

Topics: Animals; Avoidance Learning; Benzazepines; Conditioning, Operant; Dopamine Antagonists; Food Preferences; Lithium Chloride; Male; Morphine; Narcotics; Raclopride; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Saccharin; Time Factors; Water Deprivation

Rats learn to avoid palatable saccharin solutions that predict the systemic administration of reinforcing drugs as well as malaise-inducing lithium chloride (conditioned saccharin avoidance, CSA). In the present study the involvement of dopamine (DA) transmission in the acquisition of morphine, nicotine and lithium-conditioned CSA was investigated in a two-bottle choice paradigm. Nicotine tartrate (0.2 and 0.4 mg/kg s.c.) administered 15 min after saccharin presentation induced CSA, with a maximum effect at 0.4 mg/kg. The DA D1 receptor antagonist, SCH 39166 (0.1 mg/kg s.c.) and the DA D2 receptor antagonist raclopride (0.3 mg/kg s.c.), administered immediately after saccharin, prevented CSA induced by the lower but not by the higher dose of nicotine. However, combined administration of the two antagonists prevented CSA induced by the higher dose of nicotine. SCH 39166 prevented CSA induced by all morphine doses while raclopride prevented only CSA induced by the lowest dose of morphine (1.75 mg/kg). CSA induced by different doses of lithium given by the same schedule of drug-CSA (i.e. two pairings, 15 min after saccharin) was not affected by SCH 39166. However SCH 39166 impaired the acquisition of lithium-CSA when lithium was given 60 min after saccharin. In contrast, raclopride failed to affect lithium-CSA independently from the delay between saccharin and lithium. These results suggest that DA can play different roles in drug- and in lithium-CSA and are consistent with a different mechanism of drug- as compared to lithium-CSA.

Topics: Analysis of Variance; Animals; Avoidance Learning; Benzazepines; Conditioning, Operant; Dopamine; Dopamine Antagonists; Drug Interactions; Eating; Lithium Chloride; Male; Nicotine; Nicotinic Agonists; Raclopride; Rats; Rats, Sprague-Dawley; Saccharin

The role of dopamine (DA) in associative learning was studied in a conditioned taste aversion (CTA) paradigm with sucrose as the conditioned stimulus (CS) and intraperitoneal lithium chloride as the unconditioned stimulus (US). Drinking on trial of a 15% sucrose solution followed 1 h later by lithium chloride (20 or 40 mg/kg i.p.) resulted in mild CTA, as shown by reduction of drinking of the sucrose solution 24 h later. Amphetamine sulphate (0.125, 0.25, 0.50 and 1.0 mg/kg s.c.), administered on trial 5 min after sucrose drinking, facilitated CTA with maximal effects at 0.25 mg/kg s.c. Amphetamine given in the absence of lithium or 45 min after sucrose did not affect sucrose intake. The DA D1 receptor antagonist SCH 39166, administered before amphetamine either systemically (0.0125 mg/kg s.c.) or in the nucleus accumbens shell (NAc; 0.025 micro g/ micro L on each side) prevented the facilitation of CTA induced by amphetamine. It is concluded that amphetamine facilitates CTA learning by strengthening the consolidation of gustatory short-term memory via D1 receptors of the NAc shell.

Topics: Amphetamine; Animals; Avoidance Learning; Benzazepines; Central Nervous System Stimulants; Conditioning, Classical; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Interactions; Eating; Lithium Chloride; Male; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Sucrose; Taste

The involvement of dopamine (DA) in conditioned taste aversion (CTA) learning was studied with saccharin or sucrose as the conditioned stimulus (CS) and intraperitoneal lithium as the unconditioned stimulus (US). The dopamine D(1) antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390) (12.5-50 microg/kg, s.c.), given 5 min after the CS, impaired the acquisition of CTA in a paradigm consisting of three or a single CS-lithium association. SCH 23390 failed to impair CTA acquisition given 45 min after, 30 min before, or right before the CS. (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5a-benzo-(d)-naphtho-(2,1b) azepine (SCH 39166) (12.5-50.0 microg/kg, s.c), a SCH 23390 analog that does not bind to 5HT(2) receptors, also impaired CTA. No significant impairment of CTA was obtained after administration of the specific D(2)/D(3) antagonist raclopride (100 and 300 microg/kg, s.c.). The ability of SCH 23390 to impair CTA learning was confirmed by its ability to reduce the conditional aversive reactions to a gustatory CS (sweet chocolate) as estimated in a taste reactivity paradigm. SCH 39166 impaired CTA also when infused in the nucleus accumbens (NAc) shell 5 min after the CS. No impairment was obtained from the NAc core or from the bed nucleus stria terminalis. The results indicate that D(1) receptor blockade impairs CTA learning by disrupting the formation of a short-term memory trace of the gustatory CS and that endogenous dopamine acting on D(1) receptors in the NAc shell plays a role in short-term memory processes related to associative gustatory learning.

Topics: Animals; Avoidance Learning; Benzazepines; Cacao; Conditioning, Classical; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Administration Routes; Lithium Chloride; Male; Microinjections; Nucleus Accumbens; Raclopride; Rats; Receptors, Dopamine D1; Saccharin; Sucrose; Taste; Time Factors