Dopamine (DA) D3 receptors have been suggested to play a role in mechanisms underlying the ability of drug-associated cues to induce drug-seeking behaviour. The present study investigated whether SB-277011-A, a selective DA D3 receptor antagonist, modulates reinstatement of cocaine-seeking behaviour induced by cocaine-associated stimuli. The study also explored whether or not this modulation is generable to seeking behaviours associated with a nutritive reinforcer such as sucrose. Separate groups of rats were trained to associate discriminative stimuli (SD) with the availability of cocaine or sucrose pellets vs. non-reward under a FR1 schedule of reinforcement. Each reinforced response was followed by a response-cue signalling a 20-s time-out (TO). After the self-administration training criterion was met, rats underwent extinction during which cocaine, sucrose pellets and SDs were withheld. Reinstatement tests, separated by 3 d during which rates of responding under extinction conditions remained at the criterion, were performed by presenting SDs non-contingently together with the contingent presentation of response-cues signalling a 20-s TO. Within- and between-subjects experimental designs revealed that 10 and 30 mg/kg SB-277011-A attenuated reinstatement of cocaine-seeking. SB-277011-A (10 mg/kg) did not modify conditioned reinstatement triggered by sucrose pellet-associated cues. These results, provided they can be extrapolated to abstinent human addicts, suggest the potential therapeutic use of selective DA D3 receptor antagonists for the prevention of cue-controlled cocaine-seeking and relapse.

In the vertebrate brain, inhibition is largely mediated by γ-aminobutyric acid (GABA). This neurotransmitter comprises a signaling machinery of GABA, GABA receptors, transporters, glutamate decarboxylases (gads) and 4-aminobutyrate aminotransferase (abat), and associated proteins. Chloride is intimately related to GABA receptor conductance, GABA uptake, and GADs activity. The response of target neurons to GABA stimuli is shaped by chloride-cation co-transporters (CCCs), which strictly control Cl gradient across plasma membranes. This research profiled the expression of forty genes involved in GABA signaling in the zebrafish (Danio rerio) brain, grouped brain regions and retinas. Primer pairs were developed for reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The mRNA levels of the zebrafish GABA system share similarities with that of mammals, and confirm previous studies in non-mammalian species. Proposed GABA receptors are αβγ, αβδ, αβγ, αβδ, αβγ, αβδ, αβγ and αβδ. Regional brain differences were documented. Retinal hetero- or homomeric ρ-composed GABA receptors could exist, accompanying αβγ, αβδ, αβγ, αβδ. Expression patterns of α and α were opposite, with the former being more abundant in retinas, the latter in brains. Given the stoichiometry αβγ, α- or α-containing receptors likely have different regulatory mechanisms. Different gene isoforms could originate after the rounds of genome duplication during teleost evolution. This research depicts that one isoform is generally more abundantly expressed than the other. Such observations also apply to GABA receptors, GABA transporters, GABA-related enzymes, CCCs and GABA receptor-associated proteins, whose presence further strengthens the proof of a GABA system in zebrafish.

The mechanisms underlying sex determination are astonishingly plastic. Particularly the triggers for the molecular machinery, which recalls either the male or female developmental program, are highly variable and have evolved independently and repeatedly. Fish show a huge variety of sex determination systems, including both genetic and environmental triggers. The advent of sex chromosomes is assumed to stabilize genetic sex determination. However, because sex chromosomes are notoriously cluttered with repetitive DNA and pseudogenes, the study of their evolution is hampered. Here we reconstruct the birth of a Y chromosome present in the Atlantic herring. The region is tiny (230 kb) and contains only three intact genes. The candidate male-determining gene BMPR1BBY encodes a truncated form of a BMP1B receptor, which originated by gene duplication and translocation and underwent rapid protein evolution. BMPR1BBY phosphorylates SMADs in the absence of ligand and thus has the potential to induce testis formation. The Y region also contains two genes encoding subunits of the sperm-specific Ca2+ channel CatSper required for male fertility. The herring Y chromosome conforms with a characteristic feature of many sex chromosomes, namely, suppressed recombination between a sex-determining factor and genes that are beneficial for the given sex. However, the herring Y differs from other sex chromosomes in that suppression of recombination is restricted to an ∼500-kb region harboring the male-specific and sex-associated regions. As a consequence, any degeneration on the herring Y chromosome is restricted to those genes located in the small region affected by suppressed recombination.

End-of-century CO2 levels can disturb the behaviour of marine fish. We exposed freshwater zebrafish to elevated CO2, which affected turning preferences but not activity and anxiety levels. This indicates that some behaviours of freshwater fishes can be altered by elevated CO2 in a similar manner to marine fishes.